Sdek, P., Ying, H. Q., Chang, D. L. F., Qiu, W., Zheng, H. W., Touitou, R., Allday, M. J., Xiao, Z. X. J. (December 2005) MDM2 promotes proteasome-dependent ubiquitin-independent degradation of retinoblastoma protein. Molecular Cell, 20 (5). pp. 699-708. ISSN 1097-2765
Abstract
Inactivation of retinoblastoma protein (Rb) plays a critical role in the development of human malignancies. It has been shown that Rb is degraded through a proteasome-dependent pathway, yet the mechanism is largely unclear. MDM2 is frequently found amplified and overexpressed in a variety of human tumors. In this study, we find that MDM2 promotes Rb degradation in a p roteaso me-depen dent and ubiquitin-independent manner. We show that Rb, MDM2, and the C8 subunit of the 20S proteasome interact in vitro and in vivo and that MDM2 promotes Rb-C8 interaction. Expression of wild-type MDM2, but not the mutant MDM2 defective either in Rb interaction or in RING finger domain, promotes cell cycle S phase entry independent of p53. Furthermore, MDM2 ablation results in Rb accumulation and inhibition of DNA synthesis. Taken together, these findings demonstrate that MDM2 is a critical negative regulator for Rb and suggest that MDM2 overexpression contributes to cancer development by destabilizing Rb.
| Item Type: | Paper |
|---|---|
| Uncontrolled Keywords: | RING FINGER MEDIATED SUPPRESSION TUMOR-SUPPRESSOR GAMMA-INTERFERON 20S PROTEASOME ALPHA-SUBUNIT P53 EXPRESSION RB PATHWAY Biochemistry & Molecular Biology Cell Biology |
| Subjects: | bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > MDM2 bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein ubiquitination diseases & disorders > cancer > cancer types > retinoblastoma |
| CSHL Authors: | |
| Communities: | CSHL labs > Zheng lab |
| Depositing User: | Matt Covey |
| Date: | December 2005 |
| Date Deposited: | 22 Aug 2014 19:46 |
| Last Modified: | 22 Aug 2014 19:46 |
| Related URLs: | |
| URI: | https://repository.cshl.edu/id/eprint/30708 |
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