DOI: 10.1073/pnas.95.19.11324. Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21 <sup>CIP1/WAF1</sup> and cyclin D proteins

Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21 CIP1/WAF1 and cyclin D proteins

10.1073/pnas.95.19.11324

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

Deregulation of cell proliferation is a hallmark of cancer. In many transformed cells, the cyclin A/CDK2 complex that contains S-phase kinase associated proteins 1 and 2 (SKP1 and SKP2) is highly induced. To determine the roles of this complex in the cell cycle regulation and transformation, we have examined the composition of this complex. We report here that this complex contained an additional protein, human CUL-1, a member of the cullin/CDC53 family. The identification of CUL-1 as a member of the complex raises the possibility that the p19 SKP1 /p45 SKP2 /CUL-1 complex may function as the yeast SKP1-CDC53-F-box (SCF) protein complex that acts as a ubiquitin E3 ligase to regulate the G 1 /S transition. In mammalian cells, cyclin D, p21 CIP1/WAF1 , and p27 KIP1 are short-lived proteins that are controlled by ubiquitin-dependent proteolysis. To determine the potential in vivo targets of the p19 SKP1 /p45 SKP2 /CUL-1 complex, we have used the specific antisense oligodeoxynucleotides against either SKP1, SKP2, or CUL-1 RNA to inhibit their expression. Treatment of cells with these oligonucleotides caused the selective accumulation of p21 and cyclin D proteins. The protein level of p27 was not affected. These data suggest that the human p19 SKP1 /p45 SKP2 /CUL-1 complex is likely to function as an E3 ligase to selectively target cyclin D and p21 for the ubiquitin-dependent protein degradation. Aberrant expression of human p19 SKP1 /p45 SKP2 /CUL-1 complex thus may contribute to tumorigenesis by regulating the protein levels of G 1 cell cycle regulators.

Bibliography

Yu, Z.-K., Gervais, J. L. M., & Zhang, H. (1998). Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21 CIP1/WAF1 and cyclin D proteins. Proceedings of the National Academy of Sciences, 95(19), 11324â11329.

Authors 3

Zhong-Kang Yu (first)
Jennifer L. M. Gervais (additional)
Hui Zhang (additional)

References 25 Referenced 331

Dates

Type	When
Created	23 years ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 3:59 p.m.)
Indexed	1 day, 12 hours ago (Aug. 23, 2025, 12:58 a.m.)
Issued	26 years, 11 months ago (Sept. 15, 1998)
Published	26 years, 11 months ago (Sept. 15, 1998)
Published Online	26 years, 11 months ago (Sept. 15, 1998)
Published Print	26 years, 11 months ago (Sept. 15, 1998)

Funders 0

None

BibTeX

@article{Yu_1998, title={Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21 CIP1/WAF1 and cyclin D proteins}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.19.11324}, DOI={10.1073/pnas.95.19.11324}, number={19}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Yu, Zhong-Kang and Gervais, Jennifer L. M. and Zhang, Hui}, year={1998}, month=sep, pages={11324–11329} }

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