DOI: 10.1101/gad.827200. Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression

Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression

10.1101/gad.827200

Crossref journal-article

Cold Spring Harbor Laboratory

Genes & Development (246)

Abstract

The c-Myc oncoprotein plays an important role in the growth and proliferation of normal and neoplastic cells. To execute these actions, c-Myc is thought to regulate functionally diverse sets of genes that directly govern cellular mass and progression through critical cell cycle transitions. Here, we provide several lines of evidence that c-Myc promotes ubiquitin-dependent proteolysis by directly activating expression of the Cul1 gene, encoding a critical component of the ubiquitin ligase SCFSKP2. The cell cycle inhibitor p27kip1 is a known target of the SCFSKP2 complex, and Myc-induced Cul1 expression matched well with the kinetics of declining p27kip1 protein. Enforced Cul1 expression or antisense neutralization of p27kip1 was capable of overcoming the slow-growth phenotype of c-Myc null primary mouse embryonic fibroblasts (MEFs). In reconstitution assays, the addition of in vitro translated Cul1 protein alone was able to restore p27kip1ubiquitination and degradation in lysates derived fromc-myc−/− MEFs or density-arrested human fibroblasts. These functional and biochemical data provide a direct link between c-Myc transcriptional regulation and ubiquitin-mediated proteolysis and together support the view that c-Myc promotes G1 exit in part via Cul1-dependent ubiquitination and degradation of the CDK inhibitor, p27kip1.

Bibliography

OâHagan, R. C., Ohh, M., David, G., de Alboran, I. M., Alt, F. W., Kaelin, W. G., & DePinho, R. A. (2000). Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression. Genes & Development, 14(17), 2185â2191.

Authors 7

Rónán C. O'Hagan (first)
Michael Ohh (additional)
Gregory David (additional)
Ignacio Moreno de Alboran (additional)
Frederick W. Alt (additional)
William G. Kaelin (additional)
Ronald A. DePinho (additional)

References 44 Referenced 159

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Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 8 p.m.)
Deposited	3 years, 9 months ago (Nov. 14, 2021, 10:35 p.m.)
Indexed	1 month, 2 weeks ago (July 11, 2025, 6:41 a.m.)
Issued	24 years, 11 months ago (Sept. 1, 2000)
Published	24 years, 11 months ago (Sept. 1, 2000)
Published Online	24 years, 11 months ago (Sept. 1, 2000)
Published Print	24 years, 11 months ago (Sept. 1, 2000)

Funders 0

None

BibTeX

@article{O_Hagan_2000, title={Myc-enhanced expression of Cul1 promotes ubiquitin-dependent proteolysis and cell cycle progression}, volume={14}, ISSN={1549-5477}, url={http://dx.doi.org/10.1101/gad.827200}, DOI={10.1101/gad.827200}, number={17}, journal={Genes & Development}, publisher={Cold Spring Harbor Laboratory}, author={O’Hagan, Rónán C. and Ohh, Michael and David, Gregory and de Alboran, Ignacio Moreno and Alt, Frederick W. and Kaelin, William G. and DePinho, Ronald A.}, year={2000}, month=sep, pages={2185–2191} }

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