DOI: 10.1083/jcb.138.6.1219. Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2

Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2

10.1083/jcb.138.6.1219

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

The oncogene bcl-2 encodes a 26-kD protein localized to intracellular membranes, including the ER, mitochondria, and perinuclear membrane, but its mechanism of action is unknown. We have been investigating the hypothesis that Bcl-2 regulates the movement of calcium ions (Ca2+) through the ER membrane. Earlier findings in this laboratory indicated that Bcl-2 reduces Ca2+ efflux from the ER lumen in WEHI7.2 lymphoma cells treated with the Ca2+-ATPase inhibitor thapsigargin (TG) but does not prevent capacitative entry of extracellular calcium. In this report, we show that sustained elevation of cytosolic Ca2+ due to capacitative entry is not required for induction of apoptosis by TG, suggesting that ER calcium pool depletion may trigger apoptosis. Bcl-2 overexpression maintains Ca2+ uptake in the ER of TG-treated cells and prevents a TG-imposed delay in intralumenal processing of the endogenous glycoprotein cathepsin D. Also, Bcl-2 overexpression preserves the ER Ca2+ pool in untreated cells when extracellular Ca2+ is low. However, low extracellular Ca2+ reduces the antiapoptotic action of Bcl-2, suggesting that cytosolic Ca2+ elevation due to capacitative entry may be required for optimal ER pool filling and apoptosis inhibition by Bcl-2. In summary, the findings suggest that Bcl-2 maintains Ca2+ homeostasis within the ER, thereby inhibiting apoptosis induction by TG.

Bibliography

He, H., Lam, M., McCormick, T. S., & Distelhorst, C. W. (1997). Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2. The Journal of Cell Biology, 138(6), 1219â1228.

Authors 4

Huiling He (first)
Minh Lam (additional)
Thomas S. McCormick (additional)
Clark W. Distelhorst (additional)

References 50 Referenced 241

10.1016/S0021-9258(18)53280-4 / J Biol Chem / Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production by Baffy (1993)
10.1152/ajpcell.1997.272.4.C1241 / Am J Physiol / Roles of cytoplasmic Ca2+ and intracellular Ca2+stores in induction and suppression of apoptosis in S49 cells by Bian (1997)
10.1016/0092-8674(89)90019-6 / Cell / Perturbation of cellular calcium induces secretion of luminal ER proteins by Booth (1989)
10.1146/annurev.ph.52.030190.003045 / Annu Rev Physiol / Calcium-dependent regulation of protein synthesis in intact mammalian cells by Brostrom (1990)
10.1084/jem.179.4.1317 / J Exp Med / Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes by Casciola-Rosen (1994)
10.1016/S0021-9258(19)76504-1 / J Biol Chem / GTP- and inositol 1,4,5-trisphosphate-activated intracellular calcium movements in neuronal and smooth muscle cell lines by Chueh (1987)
10.1016/0092-8674(95)90408-5 / Cell / Calcium signaling by Clapham (1995)
10.1146/annurev.iy.13.040195.002501 / Annu Rev Immunol / Regulation of lymphocyte survival by the Bcl-2 gene family by Cory (1995)
10.1002/j.1460-2075.1996.tb00760.x / EMBO (Eur Mol Biol Organ) J / Cathepsin D protease mediates programmed cell death induced by interferon-γ, Fas/APO-1 and TNF-α by Deiss (1996)
10.1016/S0143-4160(96)90056-1 / Cell Calcium / Bcl-2 acts subsequent to and independent of calcium fluxes to inhibit apoptosis in thapsigargin- and glucocorticoid-treated mouse lymphoma cells by Distelhorst (1996)
{'key': '2023072207070236100_B11', 'first-page': '2051', 'article-title': 'Bcl-2 inhibits hydrogen peroxide-induced ER Ca2+pool depletion', 'volume': '12', 'author': 'Distelhorst', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / Bcl-2 inhibits hydrogen peroxide-induced ER Ca2+pool depletion by Distelhorst (1996)
{'key': '2023072207070236100_B12', 'first-page': '1843', 'article-title': 'Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes', 'volume': '6', 'author': 'Dowd', 'year': '1992', 'journal-title': 'Mol Endocrinol'} / Mol Endocrinol / Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes by Dowd (1992)
10.1083/jcb.105.5.1937 / J Cell Biol / Expression of human cathepsin D in Xenopusoocytes: phosphorylation and intracellular targeting by Faust (1987)
{'key': '2023072207070236100_B14', 'first-page': '6167', 'article-title': 'The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin', 'volume': '54', 'author': 'Furuya', 'year': '1994', 'journal-title': 'Cancer Res'} / Cancer Res / The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin by Furuya (1994)
10.1038/355033a0 / Nature (Lond) / Protein folding in the cell by Gething (1992)
10.1016/0092-8674(93)80066-N / Cell / Bcl-2 functions in an antioxidant pathway to prevent apoptosis by Hockenbery (1993)
10.1038/374814a0 / Nature (Lond) / Programmed cell death and Bcl-2 protection in very low oxygen by Jacobson (1995)
10.1006/excr.1994.1121 / Exp Cell Res / Intracellular Ca2+ signals activate apoptosis in thymocytes: studies using the Ca2+-ATPase inhibitor thapsigargin by Jiang (1994)
10.1126/science.8235659 / Science (Wash DC) / Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species by Kane (1993)
10.1073/pnas.91.14.6569 / Proc Natl Acad Sci USA / Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+fluxes by Lam (1994)
10.1182/blood.V79.12.3285.bloodjournal79123285 / Blood / Preferential synthesis of the 78-Kd glucose-regulated protein in glucocorticoid-treated S49 mouse lymphoma cells by Lam (1992)
10.1016/S0021-9258(19)50300-3 / J Biol Chem / Transcription of the grp78 promoter by Ca2+ depletion: a comparative analysis with A23187 and the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin by Li (1993)
{'key': '2023072207070236100_B23', 'first-page': '3446', 'article-title': 'Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment', 'volume': '11', 'author': 'Li', 'year': '1991', 'journal-title': 'Mol Cell Biol'} / Mol Cell Biol / Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment by Li (1991)
10.1074/jbc.270.16.9526 / J Biol Chem / Generation of a mammalian cell line deficient in glucose-regulated protein stress induction through targeted ribozyme driven by a stress-inducible promoter by Little (1995)
10.1016/S0021-9258(18)42340-X / J Biol Chem / Calcium is required for folding of newly made subunits of the asialoglycoprotein receptor within the endoplasmic reticulum by Lodish (1992)
10.1016/0304-4157(92)90033-7 / Biochim Biophys Acta / Diptheria toxin: membrane interaction and membrane translocation by London (1992)
10.1016/S0021-9258(19)47340-7 / J Biol Chem / Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps by Lytton (1991)
10.1006/bbrc.1994.2429 / Biochem Biophys Res Commun / Bcl-2 overexpression abolishes early calcium waving preceding apoptosis in NIH-3T3 murine fibroblasts by Magnelli (1994)
{'key': '2023072207070236100_B29', 'first-page': '2259', 'article-title': 'Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+', 'volume': '12', 'author': 'Marin', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+ by Marin (1996)
10.1093/oxfordjournals.jbchem.a134633 / J Biochem / Detection of calcium binding proteins by 45Ca autoradiography on nitrocellulose membrane after sodium dodecyl sulfate gel electrophoresis by Maruyama (1984)
10.1074/jbc.272.9.6087 / J Biol Chem / Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium mediated grp78/grp94 stress response by McCormick (1997)
10.1038/385353a0 / Nature (Lond) / Bcl-xL forms an ion channel in synthetic lipid membranes by Minn (1997)
10.1038/381335a0 / Nature (Lond) / X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death by Muchmore (1996)
10.1073/pnas.93.18.9893 / Proc Natl Acad Sci USA / Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria by Murphy (1996)
{'key': '2023072207070236100_B35', 'first-page': '995', 'article-title': 'Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signaling', 'volume': '55', 'author': 'Muschel', 'year': '1995', 'journal-title': 'Cancer Res'} / Cancer Res / Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signaling by Muschel (1995)
10.1002/ana.410320708 / Ann Neurol / Calcium ions and oxidative cell injury by Orrenius (1992)
10.1002/j.1460-2075.1993.tb05666.x / EMBO (Eur Mol Biol Organ) J / Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death) by Peitsch (1993)
10.1126/science.273.5283.1875 / Science (Wash DC) / Conformational states of the nuclear pore complex induced by depletion of nuclear Ca2+stores by Perez-Terzic (1996)
10.1016/0143-4160(90)90016-N / Cell Calcium / Capacitative calcium entry revisited by Putney (1990)
10.1016/0092-8674(93)80061-I / Cell / The signal for capacitative calcium entry by Putney (1993)
10.1074/jbc.271.44.27739 / J Biol Chem / Intracellular calcium stores are not required for Bcl-2-mediated protection from apoptosis by Reynolds (1996)
10.1016/0092-8674(90)90798-J / Cell / The involvement of calcium in transport of secretory proteins from the endoplasmic reticulum by Sambrook (1990)
10.1038/374811a0 / Nature (Lond) / Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL by Shimizu (1995)
10.1073/pnas.90.11.4986 / Proc Natl Acad Sci USA / Intracellular Ca2+pool content is linked to control of cell growth by Short (1993)
10.1073/pnas.87.7.2466 / Proc Natl Acad Sci USA / Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase by Thastrup (1990)
10.1016/S0076-6879(89)72017-6 / Methods Enzymol / Measurement of cytosolic free Ca2+with Quin2 by Tsien (1989)
10.1074/jbc.270.20.11955 / J Biol Chem / Thapsigargin-resistant intracellular calcium pumps: role in calcium pool function and growth of thapsigargin-resistant cells by Waldron (1995)
10.1182/blood.V88.2.386.bloodjournal882386 / Blood / Molecular thanatopsis: a discourse on the BCL2 family and cell death by Yang (1996)
10.1084/jem.182.2.367 / J Exp Med / Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death by Zamzami (1995)
10.1002/j.1460-2075.1996.tb00788.x / EMBO (Eur Mol Biol Organ) J / Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types by Zhu (1996)

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 12:47 p.m.)
Deposited	2 years, 1 month ago (July 22, 2023, 3:07 a.m.)
Indexed	1 week ago (Aug. 23, 2025, 12:58 a.m.)
Issued	27 years, 11 months ago (Sept. 22, 1997)
Published	27 years, 11 months ago (Sept. 22, 1997)
Published Online	27 years, 11 months ago (Sept. 22, 1997)
Published Print	27 years, 11 months ago (Sept. 22, 1997)

Funders 0

None

BibTeX

@article{He_1997, title={Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2}, volume={138}, ISSN={1540-8140}, url={http://dx.doi.org/10.1083/jcb.138.6.1219}, DOI={10.1083/jcb.138.6.1219}, number={6}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={He, Huiling and Lam, Minh and McCormick, Thomas S. and Distelhorst, Clark W.}, year={1997}, month=sep, pages={1219–1228} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        8,
        23
      ]
    ],
    "date-time": "2025-08-23T04:58:59Z",
    "timestamp": 1755925139865
  },
  "reference-count": 50,
  "publisher": "Rockefeller University Press",
  "issue": "6",
  "content-domain": {
    "domain": [
      "rupress.org"
    ],
    "crossmark-restriction": true
  },
  "published-print": {
    "date-parts": [
      [
        1997,
        9,
        22
      ]
    ]
  },
  "abstract": "<jats:p>The oncogene bcl-2 encodes a 26-kD protein localized to intracellular membranes, including the ER, mitochondria, and perinuclear membrane, but its mechanism of action is unknown. We have been investigating the hypothesis that Bcl-2 regulates the movement of calcium ions (Ca2+) through the ER membrane. Earlier findings in this laboratory indicated that Bcl-2 reduces Ca2+ efflux from the ER lumen in WEHI7.2 lymphoma cells treated with the Ca2+-ATPase inhibitor thapsigargin (TG) but does not prevent capacitative entry of extracellular calcium. In this report, we show that sustained elevation of cytosolic Ca2+ due to capacitative entry is not required for induction of apoptosis by TG, suggesting that ER calcium pool depletion may trigger apoptosis. Bcl-2 overexpression maintains Ca2+ uptake in the ER of TG-treated cells and prevents a TG-imposed delay in intralumenal processing of the endogenous glycoprotein cathepsin D. Also, Bcl-2 overexpression preserves the ER Ca2+ pool in untreated cells when extracellular Ca2+ is low. However, low extracellular Ca2+ reduces the antiapoptotic action of Bcl-2, suggesting that cytosolic Ca2+ elevation due to capacitative entry may be required for optimal ER pool filling and apoptosis inhibition by Bcl-2. In summary, the findings suggest that Bcl-2 maintains Ca2+ homeostasis within the ER, thereby inhibiting apoptosis induction by TG.</jats:p>",
  "DOI": "10.1083/jcb.138.6.1219",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        7,
        26
      ]
    ],
    "date-time": "2002-07-26T16:47:50Z",
    "timestamp": 1027702070000
  },
  "page": "1219-1228",
  "update-policy": "http://dx.doi.org/10.1083/jcb.crossmarkpolicy",
  "source": "Crossref",
  "is-referenced-by-count": 241,
  "title": "Maintenance of Calcium Homeostasis in the Endoplasmic Reticulum by Bcl-2",
  "prefix": "10.1083",
  "volume": "138",
  "author": [
    {
      "given": "Huiling",
      "family": "He",
      "sequence": "first",
      "affiliation": [
        {
          "name": "Departments of Medicine and Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106"
        }
      ]
    },
    {
      "given": "Minh",
      "family": "Lam",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Medicine and Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106"
        }
      ]
    },
    {
      "given": "Thomas S.",
      "family": "McCormick",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Medicine and Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106"
        }
      ]
    },
    {
      "given": "Clark W.",
      "family": "Distelhorst",
      "sequence": "additional",
      "affiliation": [
        {
          "name": "Departments of Medicine and Pharmacology, Case Western Reserve University, Cleveland, Ohio 44106"
        }
      ]
    }
  ],
  "member": "291",
  "published-online": {
    "date-parts": [
      [
        1997,
        9,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "2023072207070236100_B1",
      "doi-asserted-by": "crossref",
      "first-page": "6511",
      "DOI": "10.1016/S0021-9258(18)53280-4",
      "article-title": "Apoptosis induced by withdrawal of interleukin-3 (IL-3) from an IL-3-dependent hematopoietic cell line is associated with repartitioning of intracellular calcium and is blocked by enforced Bcl-2 oncoprotein production",
      "volume": "268",
      "author": "Baffy",
      "year": "1993",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B2",
      "doi-asserted-by": "crossref",
      "first-page": "C1241",
      "DOI": "10.1152/ajpcell.1997.272.4.C1241",
      "article-title": "Roles of cytoplasmic Ca2+ and intracellular Ca2+stores in induction and suppression of apoptosis in S49 cells",
      "volume": "272",
      "author": "Bian",
      "year": "1997",
      "journal-title": "Am J Physiol"
    },
    {
      "key": "2023072207070236100_B3",
      "doi-asserted-by": "crossref",
      "first-page": "729",
      "DOI": "10.1016/0092-8674(89)90019-6",
      "article-title": "Perturbation of cellular calcium induces secretion of luminal ER proteins",
      "volume": "59",
      "author": "Booth",
      "year": "1989",
      "journal-title": "Cell"
    },
    {
      "key": "2023072207070236100_B4",
      "doi-asserted-by": "crossref",
      "first-page": "577",
      "DOI": "10.1146/annurev.ph.52.030190.003045",
      "article-title": "Calcium-dependent regulation of protein synthesis in intact mammalian cells",
      "volume": "52",
      "author": "Brostrom",
      "year": "1990",
      "journal-title": "Annu Rev Physiol"
    },
    {
      "key": "2023072207070236100_B5",
      "doi-asserted-by": "crossref",
      "first-page": "1317",
      "DOI": "10.1084/jem.179.4.1317",
      "article-title": "Autoantigens targeted in systemic lupus erythematosus are clustered in two populations of surface structures on apoptotic keratinocytes",
      "volume": "179",
      "author": "Casciola-Rosen",
      "year": "1994",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2023072207070236100_B6",
      "doi-asserted-by": "crossref",
      "first-page": "13857",
      "DOI": "10.1016/S0021-9258(19)76504-1",
      "article-title": "GTP- and inositol 1,4,5-trisphosphate-activated intracellular calcium movements in neuronal and smooth muscle cell lines",
      "volume": "262",
      "author": "Chueh",
      "year": "1987",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B7",
      "doi-asserted-by": "crossref",
      "first-page": "259",
      "DOI": "10.1016/0092-8674(95)90408-5",
      "article-title": "Calcium signaling",
      "volume": "80",
      "author": "Clapham",
      "year": "1995",
      "journal-title": "Cell"
    },
    {
      "key": "2023072207070236100_B8",
      "doi-asserted-by": "crossref",
      "first-page": "513",
      "DOI": "10.1146/annurev.iy.13.040195.002501",
      "article-title": "Regulation of lymphocyte survival by the Bcl-2 gene family",
      "volume": "13",
      "author": "Cory",
      "year": "1995",
      "journal-title": "Annu Rev Immunol"
    },
    {
      "key": "2023072207070236100_B9",
      "doi-asserted-by": "crossref",
      "first-page": "3861",
      "DOI": "10.1002/j.1460-2075.1996.tb00760.x",
      "article-title": "Cathepsin D protease mediates programmed cell death induced by interferon-\u03b3, Fas/APO-1 and TNF-\u03b1",
      "volume": "15",
      "author": "Deiss",
      "year": "1996",
      "journal-title": "EMBO (Eur Mol Biol Organ) J"
    },
    {
      "key": "2023072207070236100_B10",
      "doi-asserted-by": "crossref",
      "first-page": "473",
      "DOI": "10.1016/S0143-4160(96)90056-1",
      "article-title": "Bcl-2 acts subsequent to and independent of calcium fluxes to inhibit apoptosis in thapsigargin- and glucocorticoid-treated mouse lymphoma cells",
      "volume": "19",
      "author": "Distelhorst",
      "year": "1996",
      "journal-title": "Cell Calcium"
    },
    {
      "key": "2023072207070236100_B11",
      "first-page": "2051",
      "article-title": "Bcl-2 inhibits hydrogen peroxide-induced ER Ca2+pool depletion",
      "volume": "12",
      "author": "Distelhorst",
      "year": "1996",
      "journal-title": "Oncogene"
    },
    {
      "key": "2023072207070236100_B12",
      "first-page": "1843",
      "article-title": "Stable expression of the calbindin-D28K complementary DNA interferes with the apoptotic pathway in lymphocytes",
      "volume": "6",
      "author": "Dowd",
      "year": "1992",
      "journal-title": "Mol Endocrinol"
    },
    {
      "key": "2023072207070236100_B13",
      "doi-asserted-by": "crossref",
      "first-page": "1937",
      "DOI": "10.1083/jcb.105.5.1937",
      "article-title": "Expression of human cathepsin D in Xenopusoocytes: phosphorylation and intracellular targeting",
      "volume": "105",
      "author": "Faust",
      "year": "1987",
      "journal-title": "J Cell Biol"
    },
    {
      "key": "2023072207070236100_B14",
      "first-page": "6167",
      "article-title": "The role of calcium, pH, and cell proliferation in the programmed (apoptotic) death of androgen-independent prostatic cancer cells induced by thapsigargin",
      "volume": "54",
      "author": "Furuya",
      "year": "1994",
      "journal-title": "Cancer Res"
    },
    {
      "key": "2023072207070236100_B15",
      "doi-asserted-by": "crossref",
      "first-page": "33",
      "DOI": "10.1038/355033a0",
      "article-title": "Protein folding in the cell",
      "volume": "355",
      "author": "Gething",
      "year": "1992",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072207070236100_B16",
      "doi-asserted-by": "crossref",
      "first-page": "241",
      "DOI": "10.1016/0092-8674(93)80066-N",
      "article-title": "Bcl-2 functions in an antioxidant pathway to prevent apoptosis",
      "volume": "75",
      "author": "Hockenbery",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072207070236100_B17",
      "doi-asserted-by": "crossref",
      "first-page": "814",
      "DOI": "10.1038/374814a0",
      "article-title": "Programmed cell death and Bcl-2 protection in very low oxygen",
      "volume": "374",
      "author": "Jacobson",
      "year": "1995",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072207070236100_B18",
      "doi-asserted-by": "crossref",
      "first-page": "84",
      "DOI": "10.1006/excr.1994.1121",
      "article-title": "Intracellular Ca2+ signals activate apoptosis in thymocytes: studies using the Ca2+-ATPase inhibitor thapsigargin",
      "volume": "212",
      "author": "Jiang",
      "year": "1994",
      "journal-title": "Exp Cell Res"
    },
    {
      "key": "2023072207070236100_B19",
      "doi-asserted-by": "crossref",
      "first-page": "1274",
      "DOI": "10.1126/science.8235659",
      "article-title": "Bcl-2 inhibition of neural death: decreased generation of reactive oxygen species",
      "volume": "262",
      "author": "Kane",
      "year": "1993",
      "journal-title": "Science (Wash DC)"
    },
    {
      "key": "2023072207070236100_B20",
      "doi-asserted-by": "crossref",
      "first-page": "6569",
      "DOI": "10.1073/pnas.91.14.6569",
      "article-title": "Evidence that BCL-2 represses apoptosis by regulating endoplasmic reticulum-associated Ca2+fluxes",
      "volume": "91",
      "author": "Lam",
      "year": "1994",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2023072207070236100_B21",
      "doi-asserted-by": "crossref",
      "first-page": "3285",
      "DOI": "10.1182/blood.V79.12.3285.bloodjournal79123285",
      "article-title": "Preferential synthesis of the 78-Kd glucose-regulated protein in glucocorticoid-treated S49 mouse lymphoma cells",
      "volume": "79",
      "author": "Lam",
      "year": "1992",
      "journal-title": "Blood"
    },
    {
      "key": "2023072207070236100_B22",
      "doi-asserted-by": "crossref",
      "first-page": "12003",
      "DOI": "10.1016/S0021-9258(19)50300-3",
      "article-title": "Transcription of the grp78 promoter by Ca2+ depletion: a comparative analysis with A23187 and the endoplasmic reticulum Ca2+-ATPase inhibitor thapsigargin",
      "volume": "268",
      "author": "Li",
      "year": "1993",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B23",
      "first-page": "3446",
      "article-title": "Competitive inhibition of a set of endoplasmic reticulum protein genes (GRP78, GRP94, and ERp72) retards cell growth and lowers viability after ionophore treatment",
      "volume": "11",
      "author": "Li",
      "year": "1991",
      "journal-title": "Mol Cell Biol"
    },
    {
      "key": "2023072207070236100_B24",
      "doi-asserted-by": "crossref",
      "first-page": "9526",
      "DOI": "10.1074/jbc.270.16.9526",
      "article-title": "Generation of a mammalian cell line deficient in glucose-regulated protein stress induction through targeted ribozyme driven by a stress-inducible promoter",
      "volume": "270",
      "author": "Little",
      "year": "1995",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B25",
      "doi-asserted-by": "crossref",
      "first-page": "12753",
      "DOI": "10.1016/S0021-9258(18)42340-X",
      "article-title": "Calcium is required for folding of newly made subunits of the asialoglycoprotein receptor within the endoplasmic reticulum",
      "volume": "267",
      "author": "Lodish",
      "year": "1992",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B26",
      "doi-asserted-by": "crossref",
      "first-page": "25",
      "DOI": "10.1016/0304-4157(92)90033-7",
      "article-title": "Diptheria toxin: membrane interaction and membrane translocation",
      "volume": "1113",
      "author": "London",
      "year": "1992",
      "journal-title": "Biochim Biophys Acta"
    },
    {
      "key": "2023072207070236100_B27",
      "doi-asserted-by": "crossref",
      "first-page": "17067",
      "DOI": "10.1016/S0021-9258(19)47340-7",
      "article-title": "Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps",
      "volume": "266",
      "author": "Lytton",
      "year": "1991",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B28",
      "doi-asserted-by": "crossref",
      "first-page": "84",
      "DOI": "10.1006/bbrc.1994.2429",
      "article-title": "Bcl-2 overexpression abolishes early calcium waving preceding apoptosis in NIH-3T3 murine fibroblasts",
      "volume": "204",
      "author": "Magnelli",
      "year": "1994",
      "journal-title": "Biochem Biophys Res Commun"
    },
    {
      "key": "2023072207070236100_B29",
      "first-page": "2259",
      "article-title": "Apoptosis suppression by bcl-2 is correlated with the regulation of nuclear and cytosolic Ca2+",
      "volume": "12",
      "author": "Marin",
      "year": "1996",
      "journal-title": "Oncogene"
    },
    {
      "key": "2023072207070236100_B30",
      "doi-asserted-by": "crossref",
      "first-page": "511",
      "DOI": "10.1093/oxfordjournals.jbchem.a134633",
      "article-title": "Detection of calcium binding proteins by 45Ca autoradiography on nitrocellulose membrane after sodium dodecyl sulfate gel electrophoresis",
      "volume": "95",
      "author": "Maruyama",
      "year": "1984",
      "journal-title": "J Biochem"
    },
    {
      "key": "2023072207070236100_B31",
      "doi-asserted-by": "crossref",
      "first-page": "6087",
      "DOI": "10.1074/jbc.272.9.6087",
      "article-title": "Mouse lymphoma cells destined to undergo apoptosis in response to thapsigargin treatment fail to generate a calcium mediated grp78/grp94 stress response",
      "volume": "272",
      "author": "McCormick",
      "year": "1997",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B32",
      "doi-asserted-by": "crossref",
      "first-page": "353",
      "DOI": "10.1038/385353a0",
      "article-title": "Bcl-xL forms an ion channel in synthetic lipid membranes",
      "volume": "385",
      "author": "Minn",
      "year": "1997",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072207070236100_B33",
      "doi-asserted-by": "crossref",
      "first-page": "335",
      "DOI": "10.1038/381335a0",
      "article-title": "X-ray and NMR structure of human Bcl-XL, an inhibitor of programmed cell death",
      "volume": "381",
      "author": "Muchmore",
      "year": "1996",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072207070236100_B34",
      "doi-asserted-by": "crossref",
      "first-page": "9893",
      "DOI": "10.1073/pnas.93.18.9893",
      "article-title": "Bcl-2 potentiates the maximal calcium uptake capacity of neural cell mitochondria",
      "volume": "93",
      "author": "Murphy",
      "year": "1996",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2023072207070236100_B35",
      "first-page": "995",
      "article-title": "Induction of apoptosis at different oxygen tensions: evidence that oxygen radicals do not mediate apoptotic signaling",
      "volume": "55",
      "author": "Muschel",
      "year": "1995",
      "journal-title": "Cancer Res"
    },
    {
      "key": "2023072207070236100_B36",
      "doi-asserted-by": "crossref",
      "first-page": "S33",
      "DOI": "10.1002/ana.410320708",
      "article-title": "Calcium ions and oxidative cell injury",
      "volume": "32",
      "author": "Orrenius",
      "year": "1992",
      "journal-title": "Ann Neurol"
    },
    {
      "key": "2023072207070236100_B37",
      "doi-asserted-by": "crossref",
      "first-page": "371",
      "DOI": "10.1002/j.1460-2075.1993.tb05666.x",
      "article-title": "Characterization of the endogenous deoxyribonuclease involved in nuclear DNA degradation during apoptosis (programmed cell death)",
      "volume": "12",
      "author": "Peitsch",
      "year": "1993",
      "journal-title": "EMBO (Eur Mol Biol Organ) J"
    },
    {
      "key": "2023072207070236100_B38",
      "doi-asserted-by": "crossref",
      "first-page": "1875",
      "DOI": "10.1126/science.273.5283.1875",
      "article-title": "Conformational states of the nuclear pore complex induced by depletion of nuclear Ca2+stores",
      "volume": "273",
      "author": "Perez-Terzic",
      "year": "1996",
      "journal-title": "Science (Wash DC)"
    },
    {
      "key": "2023072207070236100_B39",
      "doi-asserted-by": "crossref",
      "first-page": "611",
      "DOI": "10.1016/0143-4160(90)90016-N",
      "article-title": "Capacitative calcium entry revisited",
      "volume": "11",
      "author": "Putney",
      "year": "1990",
      "journal-title": "Cell Calcium"
    },
    {
      "key": "2023072207070236100_B40",
      "doi-asserted-by": "crossref",
      "first-page": "199",
      "DOI": "10.1016/0092-8674(93)80061-I",
      "article-title": "The signal for capacitative calcium entry",
      "volume": "75",
      "author": "Putney",
      "year": "1993",
      "journal-title": "Cell"
    },
    {
      "key": "2023072207070236100_B41",
      "doi-asserted-by": "crossref",
      "first-page": "27739",
      "DOI": "10.1074/jbc.271.44.27739",
      "article-title": "Intracellular calcium stores are not required for Bcl-2-mediated protection from apoptosis",
      "volume": "271",
      "author": "Reynolds",
      "year": "1996",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B42",
      "doi-asserted-by": "crossref",
      "first-page": "197",
      "DOI": "10.1016/0092-8674(90)90798-J",
      "article-title": "The involvement of calcium in transport of secretory proteins from the endoplasmic reticulum",
      "volume": "61",
      "author": "Sambrook",
      "year": "1990",
      "journal-title": "Cell"
    },
    {
      "key": "2023072207070236100_B43",
      "doi-asserted-by": "crossref",
      "first-page": "811",
      "DOI": "10.1038/374811a0",
      "article-title": "Prevention of hypoxia-induced cell death by Bcl-2 and Bcl-xL",
      "volume": "374",
      "author": "Shimizu",
      "year": "1995",
      "journal-title": "Nature (Lond)"
    },
    {
      "key": "2023072207070236100_B44",
      "doi-asserted-by": "crossref",
      "first-page": "4986",
      "DOI": "10.1073/pnas.90.11.4986",
      "article-title": "Intracellular Ca2+pool content is linked to control of cell growth",
      "volume": "90",
      "author": "Short",
      "year": "1993",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2023072207070236100_B45",
      "doi-asserted-by": "crossref",
      "first-page": "2466",
      "DOI": "10.1073/pnas.87.7.2466",
      "article-title": "Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2+-ATPase",
      "volume": "87",
      "author": "Thastrup",
      "year": "1990",
      "journal-title": "Proc Natl Acad Sci USA"
    },
    {
      "key": "2023072207070236100_B46",
      "doi-asserted-by": "crossref",
      "first-page": "230",
      "DOI": "10.1016/S0076-6879(89)72017-6",
      "article-title": "Measurement of cytosolic free Ca2+with Quin2",
      "volume": "172",
      "author": "Tsien",
      "year": "1989",
      "journal-title": "Methods Enzymol"
    },
    {
      "key": "2023072207070236100_B47",
      "doi-asserted-by": "crossref",
      "first-page": "11955",
      "DOI": "10.1074/jbc.270.20.11955",
      "article-title": "Thapsigargin-resistant intracellular calcium pumps: role in calcium pool function and growth of thapsigargin-resistant cells",
      "volume": "270",
      "author": "Waldron",
      "year": "1995",
      "journal-title": "J Biol Chem"
    },
    {
      "key": "2023072207070236100_B48",
      "doi-asserted-by": "crossref",
      "first-page": "386",
      "DOI": "10.1182/blood.V88.2.386.bloodjournal882386",
      "article-title": "Molecular thanatopsis: a discourse on the BCL2 family and cell death",
      "volume": "88",
      "author": "Yang",
      "year": "1996",
      "journal-title": "Blood"
    },
    {
      "key": "2023072207070236100_B49",
      "doi-asserted-by": "crossref",
      "first-page": "367",
      "DOI": "10.1084/jem.182.2.367",
      "article-title": "Sequential reduction of mitochondrial transmembrane potential and generation of reactive oxygen species in early programmed cell death",
      "volume": "182",
      "author": "Zamzami",
      "year": "1995",
      "journal-title": "J Exp Med"
    },
    {
      "key": "2023072207070236100_B50",
      "doi-asserted-by": "crossref",
      "first-page": "4130",
      "DOI": "10.1002/j.1460-2075.1996.tb00788.x",
      "article-title": "Bcl-2 mutants with restricted subcellular location reveal spatially distinct pathways for apoptosis in different cell types",
      "volume": "15",
      "author": "Zhu",
      "year": "1996",
      "journal-title": "EMBO (Eur Mol Biol Organ) J"
    }
  ],
  "container-title": "The Journal of Cell Biology",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://rupress.org/jcb/article-pdf/138/6/1219/1486501/16434.pdf",
      "content-type": "application/pdf",
      "content-version": "vor",
      "intended-application": "syndication"
    },
    {
      "URL": "https://rupress.org/jcb/article-pdf/138/6/1219/1486501/16434.pdf",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        7,
        22
      ]
    ],
    "date-time": "2023-07-22T07:07:41Z",
    "timestamp": 1690009661000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://rupress.org/jcb/article/138/6/1219/704/Maintenance-of-Calcium-Homeostasis-in-the"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        1997,
        9,
        22
      ]
    ]
  },
  "references-count": 50,
  "journal-issue": {
    "issue": "6",
    "published-print": {
      "date-parts": [
        [
          1997,
          9,
          22
        ]
      ]
    }
  },
  "URL": "http://dx.doi.org/10.1083/jcb.138.6.1219",
  "relation": {},
  "ISSN": [
    "0021-9525",
    "1540-8140"
  ],
  "subject": [],
  "published": {
    "date-parts": [
      [
        1997,
        9,
        22
      ]
    ]
  }
}