DOI: 10.1101/gad.12.24.3797. c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets

c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets

10.1101/gad.12.24.3797

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

We report here that the expression of virtually all proposed c-Myc target genes is unchanged in cells containing a homozygous null deletion of c-myc. Two noteworthy exceptions are the genecad, which has reduced log phase expression and serum induction in c-myc null cells, and the growth arrest gene gadd45, which is derepressed by c-myc knockout. Thus, cad andgadd45 are the only proposed targets of c-Myc that may contribute to the dramatic slow growth phenotype of c-myc null cells. Our results demonstrate that a loss-of-function approach is critical for the evaluation of potential c-Myc target genes.

Bibliography

Bush, A., Mateyak, M., Dugan, K., Obaya, A., Adachi, S., Sedivy, J., & Cole, M. (1998). c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets. Genes & Development, 12(24), 3797â3802.

Authors 7

Andrew Bush (first)
Maria Mateyak (additional)
Kerri Dugan (additional)
Alvaro Obaya (additional)
Susumu Adachi (additional)
John Sedivy (additional)
Michael Cole (additional)

References 37 Referenced 138

10.1038/310655a0
10.1073/pnas.90.16.7804
10.1101/gad.6.12b.2513
10.1128/MCB.17.5.2529 / Mol. Cell. Biol. / Myc versus USF: Discrimination at the cad gene is determined by core promoter elements. by Boyd (1997)
10.1128/MCB.15.3.1536 / Mol. Cell. Biol. / An essential domain of the c-Myc protein interacts with a nuclear factor that is also required for E1A-mediated transformation. by Brough (1995)
10.1093/nar/24.10.1971
10.1038/340066a0
10.1002/j.1460-2075.1991.tb07929.x / EMBO J. / The MYC protein activates transcription of the α-prothymosin gene. by Eilers (1991)
10.1128/MCB.17.1.100 / Mol. Cell. Biol. / The Myc negative autoregulation mechanism requires Myc-Max association and involves the c-Myc P2 minimal promoter. by Facchini (1997)
10.1126/science.7667636
10.1038/382511a0
10.1002/j.1460-2075.1996.tb00808.x / EMBO J. / Myc-Max heterodimers activate a DEAD box gene and interact with multiple E box-related sites in vivo. by Grandori (1996)
10.1038/314366a0
10.1016/S0065-230X(08)60353-X
10.1101/gad.11.1.44
10.1128/MCB.16.9.4754 / Mol. Cell. Biol. / An essential E box in the promoter of the gene encoding the mRNA cap binding protein (eukaryotic initiation factor 4E) is a target for activation by c-myc. by Jones (1996)
10.1016/S0021-9258(17)42161-2 / J. Biol. Chem. / Start site selection at the TATA-less carbamoyl-phosphate synthase (glutamine hydrolyzing)/aspartate carbamoyltransferase/dihydroorotase promoter. by Kollmar (1994)
10.1038/359426a0
10.1128/MCB.17.9.4967 / Mol. Cell. Biol. / Identification of putative c-Myc-responsive genes: Characterization of rcl, a novel growth-related gene. by Lewis (1997)
{'key': '2021111418585975000_12.24.3797.20', 'first-page': '5510', 'article-title': 'Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis.', 'volume': '14', 'author': 'Lutterbach', 'year': '1994', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Hierarchical phosphorylation at N-terminal transformation-sensitive sites in c-Myc protein is regulated by mitogens and in mitosis. by Lutterbach (1994)
10.1016/0092-8674(87)90015-8
10.1146/annurev.bi.61.070192.004113
10.1038/sj.onc.1201138
{'key': '2021111418585975000_12.24.3797.24', 'first-page': '1039', 'article-title': 'Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination.', 'volume': '8', 'author': 'Mateyak', 'year': '1997', 'journal-title': 'Cell Growth Differ.'} / Cell Growth Differ. / Phenotypes of c-Myc-deficient rat fibroblasts isolated by targeted homologous recombination. by Mateyak (1997)
10.1016/0076-6879(93)17090-R
10.1128/MCB.15.5.2527 / Mol. Cell. Biol. / An E-Box-mediated increase in cad transcription at the G1/S-phase boundary is suppressed by inhibitory c-Myc mutants. by Miltenberger (1995)
10.1016/S0021-9258(17)37899-7 / J. Biol. Chem. / N-(Phosphonacetyl)-L-aspartate-resistant hamster cells overaccumulate a single mRNA coding for the multifunctional protein that catalyzes the first steps of UMP synthesis. by Padgett (1979)
{'key': '2021111418585975000_12.24.3797.28', 'first-page': '4961', 'article-title': 'Domains of human c-Myc protein required for autosuppression and cooperation with ras oncogenes are overlapping.', 'volume': '10', 'author': 'Penn', 'year': '1990', 'journal-title': 'Mol. Cell. Biol.'} / Mol. Cell. Biol. / Domains of human c-Myc protein required for autosuppression and cooperation with ras oncogenes are overlapping. by Penn (1990)
{'key': '2021111418585975000_12.24.3797.29', 'first-page': '57', 'article-title': 'c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif.', 'volume': '4', 'author': 'Reisman', 'year': '1993', 'journal-title': 'Cell Growth Differ.'} / Cell Growth Differ. / c-Myc trans-activates the p53 promoter through a required downstream CACGTG motif. by Reisman (1993)
10.1073/pnas.94.13.6658
10.1093/nar/22.3.427
10.1038/sj.onc.1201067
{'key': '2021111418585975000_12.24.3797.33', 'first-page': '2579', 'article-title': 'The differentiation primary response gene Myd118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21Waf1/Cip1.', 'volume': '12', 'author': 'Vairapandi', 'year': '1996', 'journal-title': 'Oncogene'} / Oncogene / The differentiation primary response gene Myd118, related to GADD45, encodes for a nuclear protein which interacts with PCNA and p21Waf1/Cip1. by Vairapandi (1996)
{'key': '2021111418585975000_12.24.3797.34', 'first-page': '879', 'article-title': 'c-Myc induces the expression and activity of ornithine decarboxylase.', 'volume': '4', 'author': 'Wagner', 'year': '1993', 'journal-title': 'Cell Growth Differ.'} / Cell Growth Differ. / c-Myc induces the expression and activity of ornithine decarboxylase. by Wagner (1993)
Xiao, Q., G. Claassen, J. Shi, S. Adachi, J. Sedivy, and S.R. Hann. 1998. Transactivation-defective c-MycS retains the ability to regulate proliferation and apoptosis. Genes & Dev. 12: (this issue).. (10.1101/gad.12.24.3803)
10.1073/pnas.84.21.7363
10.1128/MCB.14.4.2361

Dates

Type	When
Created	17 years, 6 months ago (Feb. 20, 2008, 5:15 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 10:26 p.m.)
Indexed	3 weeks, 3 days ago (Aug. 5, 2025, 8:47 a.m.)
Issued	26 years, 8 months ago (Dec. 15, 1998)
Published	26 years, 8 months ago (Dec. 15, 1998)
Published Online	26 years, 8 months ago (Dec. 15, 1998)
Published Print	26 years, 8 months ago (Dec. 15, 1998)

Funders 0

None

BibTeX

@article{Bush_1998, title={c-myc null cells misregulate cad and gadd45 but not other proposed c-Myc targets}, volume={12}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.12.24.3797}, DOI={10.1101/gad.12.24.3797}, number={24}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={Bush, Andrew and Mateyak, Maria and Dugan, Kerri and Obaya, Alvaro and Adachi, Susumu and Sedivy, John and Cole, Michael}, year={1998}, month=dec, pages={3797–3802} }

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