DOI: 10.1083/jcb.200506030. Regulation of ubiquitin ligase dynamics by the nucleolus

Regulation of ubiquitin ligase dynamics by the nucleolus

10.1083/jcb.200506030

Crossref journal-article

Rockefeller University Press

The Journal of Cell Biology (291)

Abstract

Cellular pathways relay information through dynamic protein interactions. We have assessed the kinetic properties of the murine double minute protein (MDM2) and von Hippel-Lindau (VHL) ubiquitin ligases in living cells under physiological conditions that alter the stability of their respective p53 and hypoxia-inducible factor substrates. Photobleaching experiments reveal that MDM2 and VHL are highly mobile proteins in settings where their substrates are efficiently degraded. The nucleolar architecture converts MDM2 and VHL to a static state in response to regulatory cues that are associated with substrate stability. After signal termination, the nucleolus is able to rapidly release these proteins from static detention, thereby restoring their high mobility profiles. A protein surface region of VHL's β-sheet domain was identified as a discrete [H+]-responsive nucleolar detention signal that targets the VHL/Cullin-2 ubiquitin ligase complex to nucleoli in response to physiological fluctuations in environmental pH. Data shown here provide the first evidence that cells have evolved a mechanism to regulate molecular networks by reversibly switching proteins between a mobile and static state.

Bibliography

Mekhail, K., Khacho, M., Carrigan, A., Hache, R. R. J., Gunaratnam, L., & Lee, S. (2005). Regulation of ubiquitin ligase dynamics by the nucleolus. The Journal of Cell Biology, 170(5), 733â744.

Authors 6

Karim Mekhail (first)
Mireille Khacho (additional)
Amanda Carrigan (additional)
Robert R.J. Hache (additional)
Lakshman Gunaratnam (additional)
Stephen Lee (additional)

References 56 Referenced 72

10.1083/jcb.137.7.1459 / J. Cell Biol. (1997)
10.1038/nature03207 / Nature. (2005)
10.1046/j.1432-1327.2001.02225.x / Eur. J. Biochem. (2001)
10.1126/science.1099402 / Science. (2004)
10.1074/jbc.M008295200 / J. Biol. Chem. (2001)
10.1016/S0092-8674(02)00650-5 / Cell. (2002)
10.1038/35014078 / Nat. Cell Biol. (2000)
10.1083/jcb.153.1.169 / J. Cell Biol. (2001)
10.1126/science.1078572 / Science. (2003)
10.1038/nrm1552 / Nat. Rev. Mol. Cell Biol. (2005)
10.1074/jbc.M002740200 / J. Biol. Chem. (2000)
10.1016/S0046-8177(97)90035-6 / Hum. Pathol. (1997)
10.1128/MCB.25.2.728-739.2005 / Mol. Cell. Biol. (2005)
10.1083/jcb.150.3.433 / J. Cell Biol. (2000)
10.1126/science.1076164 / Science. (2002)
10.1126/science.1078694 / Science. (2003)
10.1128/MCB.18.12.7288 / Mol. Cell. Biol. (1998)
10.1101/gad.869601 / Genes Dev. (2001)
10.1128/MCB.22.15.5319-5336.2002 / Mol. Cell. Biol. (2002)
10.1074/jbc.275.12.8991 / J. Biol. Chem. (2000)
10.1038/nrc885 / Nat. Rev. Cancer. (2002)
10.1126/science.7660130 / Science. (1995)
10.1083/jcb.153.7.1341 / J. Cell Biol. (2001)
10.1242/jcs.01736 / J. Cell Sci. (2005)
10.1128/MCB.19.2.1486 / Mol. Cell. Biol. (1999)
{'key': '2023072909444241900_BIB26', 'first-page': 'S7', 'volume': 'Suppl)', 'year': '2003', 'journal-title': 'Nat. Cell Biol.'} / Nat. Cell Biol. (2003)
10.1038/35074506 / Nat. Cell Biol. (2001)
10.1016/S1535-6108(03)00134-X / Cancer Cell. (2003)
10.1038/nrm1355 / Nat. Rev. Mol. Cell Biol. (2004)
10.1038/ncb1144 / Nat. Cell Biol. (2004)
{'key': '2023072909444241900_BIB31', 'first-page': '1027', 'volume': '3', 'year': '2004', 'journal-title': 'Cell Cycle.'} / Cell Cycle. (2004)
10.1016/S1044-579X(02)00099-8 / Semin. Cancer Biol. (2003)
10.1126/science.291.5505.843 / Science. (2001)
10.1016/0092-8674(92)90644-R / Cell. (1992)
10.1038/nrm1049 / Nat. Rev. Mol. Cell Biol. (2003)
10.1038/362857a0 / Nature. (1993)
10.1073/pnas.94.6.2156 / Proc. Natl. Acad. Sci. USA. (1997)
10.1016/S0092-8674(04)00342-3 / Cell. (2004)
{'key': '2023072909444241900_BIB39', 'first-page': '9', 'volume': '6', 'year': '2005', 'journal-title': 'Nat. Rev. Mol. Cell Biol.'} / Nat. Rev. Mol. Cell Biol. (2005)
10.1038/35007077 / Nature. (2000)
10.1038/ncb1184 / Nat. Cell Biol. (2004)
10.1093/emboj/17.2.554 / EMBO J. (1998)
10.1016/S1097-2765(01)80001-0 / Mol. Cell. (1999)
10.1101/gad.14.16.1983 / Genes Dev. (2000)
10.1016/S0092-8674(00)80733-3 / Cell. (1999)
10.1016/S1097-2765(01)00291-X / Mol. Cell. (2001)
10.1006/viro.1995.0016 / Virology. (1995)
10.1073/pnas.96.12.6937 / Proc. Natl. Acad. Sci. USA. (1999)
10.1016/S1097-2765(00)80020-9 / Mol. Cell. (1998)
10.1083/jcb.200409053 / J. Cell Biol. (2005)
10.1083/jcb.200401056 / J. Cell Biol. (2004)
10.1038/19775 / Nature. (1999)
10.1074/jbc.M306356200 / J. Biol. Chem. (2003)
10.1038/8991 / Nat. Cell Biol. (1999)
10.1128/MCB.20.7.2517-2528.2000 / Mol. Cell. Biol. (2000)
10.1038/35056563 / Nat. Rev. Mol. Cell Biol. (2001)

Dates

Type	When
Created	20 years ago (Aug. 29, 2005, 3:02 p.m.)
Deposited	2 years, 1 month ago (July 29, 2023, 5:45 a.m.)
Indexed	11 months, 2 weeks ago (Sept. 15, 2024, 5:16 a.m.)
Issued	20 years ago (Aug. 29, 2005)
Published	20 years ago (Aug. 29, 2005)
Published Online	20 years ago (Aug. 29, 2005)
Published Print	20 years ago (Aug. 29, 2005)

Funders 0

None

BibTeX

@article{Mekhail_2005, title={Regulation of ubiquitin ligase dynamics by the nucleolus}, volume={170}, ISSN={0021-9525}, url={http://dx.doi.org/10.1083/jcb.200506030}, DOI={10.1083/jcb.200506030}, number={5}, journal={The Journal of Cell Biology}, publisher={Rockefeller University Press}, author={Mekhail, Karim and Khacho, Mireille and Carrigan, Amanda and Hache, Robert R.J. and Gunaratnam, Lakshman and Lee, Stephen}, year={2005}, month=aug, pages={733–744} }

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    {
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      "first-page": "77",
      "DOI": "10.1038/nature03207",
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      "year": "2005",
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      "DOI": "10.1046/j.1432-1327.2001.02225.x",
      "volume": "268",
      "year": "2001",
      "journal-title": "Eur. J. Biochem."
    },
    {
      "key": "2023072909444241900_BIB4",
      "doi-asserted-by": "crossref",
      "first-page": "516",
      "DOI": "10.1126/science.1099402",
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    },
    {
      "key": "2023072909444241900_BIB5",
      "doi-asserted-by": "crossref",
      "first-page": "1407",
      "DOI": "10.1074/jbc.M008295200",
      "volume": "276",
      "year": "2001",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072909444241900_BIB6",
      "doi-asserted-by": "crossref",
      "first-page": "513",
      "DOI": "10.1016/S0092-8674(02)00650-5",
      "volume": "108",
      "year": "2002",
      "journal-title": "Cell."
    },
    {
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      "first-page": "E107",
      "DOI": "10.1038/35014078",
      "volume": "2",
      "year": "2000",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB8",
      "doi-asserted-by": "crossref",
      "first-page": "169",
      "DOI": "10.1083/jcb.153.1.169",
      "volume": "153",
      "year": "2001",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB9",
      "doi-asserted-by": "crossref",
      "first-page": "721",
      "DOI": "10.1126/science.1078572",
      "volume": "299",
      "year": "2003",
      "journal-title": "Science."
    },
    {
      "key": "2023072909444241900_BIB10",
      "doi-asserted-by": "crossref",
      "first-page": "79",
      "DOI": "10.1038/nrm1552",
      "volume": "6",
      "year": "2005",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB11",
      "doi-asserted-by": "crossref",
      "first-page": "25733",
      "DOI": "10.1074/jbc.M002740200",
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      "year": "2000",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072909444241900_BIB12",
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      "first-page": "459",
      "DOI": "10.1016/S0046-8177(97)90035-6",
      "volume": "28",
      "year": "1997",
      "journal-title": "Hum. Pathol."
    },
    {
      "key": "2023072909444241900_BIB13",
      "doi-asserted-by": "crossref",
      "first-page": "728",
      "DOI": "10.1128/MCB.25.2.728-739.2005",
      "volume": "25",
      "year": "2005",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072909444241900_BIB14",
      "doi-asserted-by": "crossref",
      "first-page": "433",
      "DOI": "10.1083/jcb.150.3.433",
      "volume": "150",
      "year": "2000",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB15",
      "doi-asserted-by": "crossref",
      "first-page": "1623",
      "DOI": "10.1126/science.1076164",
      "volume": "298",
      "year": "2002",
      "journal-title": "Science."
    },
    {
      "key": "2023072909444241900_BIB16",
      "doi-asserted-by": "crossref",
      "first-page": "719",
      "DOI": "10.1126/science.1078694",
      "volume": "299",
      "year": "2003",
      "journal-title": "Science."
    },
    {
      "key": "2023072909444241900_BIB17",
      "doi-asserted-by": "crossref",
      "first-page": "7288",
      "DOI": "10.1128/MCB.18.12.7288",
      "volume": "18",
      "year": "1998",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072909444241900_BIB18",
      "doi-asserted-by": "crossref",
      "first-page": "1528",
      "DOI": "10.1101/gad.869601",
      "volume": "15",
      "year": "2001",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072909444241900_BIB19",
      "doi-asserted-by": "crossref",
      "first-page": "5319",
      "DOI": "10.1128/MCB.22.15.5319-5336.2002",
      "volume": "22",
      "year": "2002",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072909444241900_BIB20",
      "doi-asserted-by": "crossref",
      "first-page": "8991",
      "DOI": "10.1074/jbc.275.12.8991",
      "volume": "275",
      "year": "2000",
      "journal-title": "J. Biol. Chem."
    },
    {
      "key": "2023072909444241900_BIB21",
      "doi-asserted-by": "crossref",
      "first-page": "673",
      "DOI": "10.1038/nrc885",
      "volume": "2",
      "year": "2002",
      "journal-title": "Nat. Rev. Cancer."
    },
    {
      "key": "2023072909444241900_BIB22",
      "doi-asserted-by": "crossref",
      "first-page": "1444",
      "DOI": "10.1126/science.7660130",
      "volume": "269",
      "year": "1995",
      "journal-title": "Science."
    },
    {
      "key": "2023072909444241900_BIB23",
      "doi-asserted-by": "crossref",
      "first-page": "1341",
      "DOI": "10.1083/jcb.153.7.1341",
      "volume": "153",
      "year": "2001",
      "journal-title": "J. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB24",
      "doi-asserted-by": "crossref",
      "first-page": "1335",
      "DOI": "10.1242/jcs.01736",
      "volume": "118",
      "year": "2005",
      "journal-title": "J. Cell Sci."
    },
    {
      "key": "2023072909444241900_BIB25",
      "doi-asserted-by": "crossref",
      "first-page": "1486",
      "DOI": "10.1128/MCB.19.2.1486",
      "volume": "19",
      "year": "1999",
      "journal-title": "Mol. Cell. Biol."
    },
    {
      "key": "2023072909444241900_BIB26",
      "first-page": "S7",
      "volume": "Suppl)",
      "year": "2003",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB27",
      "doi-asserted-by": "crossref",
      "first-page": "445",
      "DOI": "10.1038/35074506",
      "volume": "3",
      "year": "2001",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB28",
      "doi-asserted-by": "crossref",
      "first-page": "577",
      "DOI": "10.1016/S1535-6108(03)00134-X",
      "volume": "3",
      "year": "2003",
      "journal-title": "Cancer Cell."
    },
    {
      "key": "2023072909444241900_BIB29",
      "doi-asserted-by": "crossref",
      "first-page": "296",
      "DOI": "10.1038/nrm1355",
      "volume": "5",
      "year": "2004",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB30",
      "doi-asserted-by": "crossref",
      "first-page": "642",
      "DOI": "10.1038/ncb1144",
      "volume": "6",
      "year": "2004",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB31",
      "first-page": "1027",
      "volume": "3",
      "year": "2004",
      "journal-title": "Cell Cycle."
    },
    {
      "key": "2023072909444241900_BIB32",
      "doi-asserted-by": "crossref",
      "first-page": "49",
      "DOI": "10.1016/S1044-579X(02)00099-8",
      "volume": "13",
      "year": "2003",
      "journal-title": "Semin. Cancer Biol."
    },
    {
      "key": "2023072909444241900_BIB33",
      "doi-asserted-by": "crossref",
      "first-page": "843",
      "DOI": "10.1126/science.291.5505.843",
      "volume": "291",
      "year": "2001",
      "journal-title": "Science."
    },
    {
      "key": "2023072909444241900_BIB34",
      "doi-asserted-by": "crossref",
      "first-page": "1237",
      "DOI": "10.1016/0092-8674(92)90644-R",
      "volume": "69",
      "year": "1992",
      "journal-title": "Cell."
    },
    {
      "key": "2023072909444241900_BIB35",
      "doi-asserted-by": "crossref",
      "first-page": "192",
      "DOI": "10.1038/nrm1049",
      "volume": "4",
      "year": "2003",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB36",
      "doi-asserted-by": "crossref",
      "first-page": "857",
      "DOI": "10.1038/362857a0",
      "volume": "362",
      "year": "1993",
      "journal-title": "Nature."
    },
    {
      "key": "2023072909444241900_BIB37",
      "doi-asserted-by": "crossref",
      "first-page": "2156",
      "DOI": "10.1073/pnas.94.6.2156",
      "volume": "94",
      "year": "1997",
      "journal-title": "Proc. Natl. Acad. Sci. USA."
    },
    {
      "key": "2023072909444241900_BIB38",
      "doi-asserted-by": "crossref",
      "first-page": "311",
      "DOI": "10.1016/S0092-8674(04)00342-3",
      "volume": "117",
      "year": "2004",
      "journal-title": "Cell."
    },
    {
      "key": "2023072909444241900_BIB39",
      "first-page": "9",
      "volume": "6",
      "year": "2005",
      "journal-title": "Nat. Rev. Mol. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB40",
      "doi-asserted-by": "crossref",
      "first-page": "604",
      "DOI": "10.1038/35007077",
      "volume": "404",
      "year": "2000",
      "journal-title": "Nature."
    },
    {
      "key": "2023072909444241900_BIB41",
      "doi-asserted-by": "crossref",
      "first-page": "1114",
      "DOI": "10.1038/ncb1184",
      "volume": "6",
      "year": "2004",
      "journal-title": "Nat. Cell Biol."
    },
    {
      "key": "2023072909444241900_BIB42",
      "doi-asserted-by": "crossref",
      "first-page": "554",
      "DOI": "10.1093/emboj/17.2.554",
      "volume": "17",
      "year": "1998",
      "journal-title": "EMBO J."
    },
    {
      "key": "2023072909444241900_BIB43",
      "doi-asserted-by": "crossref",
      "first-page": "687",
      "DOI": "10.1016/S1097-2765(01)80001-0",
      "volume": "3",
      "year": "1999",
      "journal-title": "Mol. Cell."
    },
    {
      "key": "2023072909444241900_BIB44",
      "doi-asserted-by": "crossref",
      "first-page": "1983",
      "DOI": "10.1101/gad.14.16.1983",
      "volume": "14",
      "year": "2000",
      "journal-title": "Genes Dev."
    },
    {
      "key": "2023072909444241900_BIB45",
      "doi-asserted-by": "crossref",
      "first-page": "233",
      "DOI": "10.1016/S0092-8674(00)80733-3",
      "volume": "97",
      "year": "1999",
      "journal-title": "Cell."
    },
    {
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