JBC Avanti Polar Lipids

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

A more recent version of this article appeared on August 18, 2006
This Article
Right arrow Full Text (Accepted Manuscript)
Right arrow All Versions of this Article:
281/33/24058    most recent
M603105200v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ji, P.
Right arrow Articles by Zhu, L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ji, P.
Right arrow Articles by Zhu, L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

Papers In Press, published online ahead of print June 14, 2006
J. Biol. Chem, 10.1074/jbc.M603105200
Submitted on March 31, 2006
Revised on June 14, 2006
Accepted on June 14, 2006

SKP2 contains a novel cyclin a binding domain that directly protects cyclin A from inhibition by p27Kip1

Peng Ji, Luba Goldin, Hao Ren, Daqian Sun, Daniele Guardavaccaro, Michele Pagano, and Liang Zhu

Dev. Mol. Biol., Albert Einstein College of Medicine, Bronx, NY 10461

Corresponding Author: lizhu{at}aecom.yu.edu

Skp2 is well known as the F-box protein of the SCFSkp2Roc1 complex targeting p27 for ubiquitylation. Skp2 also forms complexes with cyclin A, which are particularly abundant in cancer cells due to frequent Skp2 overexpression, but the mechanism and significance of this interaction remain unknown. Here, we report that Skp2-cyclin A interaction is mediated by novel interaction sequences on both Skp2 and cyclin A, distinguishing it from the well-known RxL-HP interaction between cyclins and cyclin-binding proteins. Furthermore, a short peptide derived from the mapped cyclin A binding sequences of Skp2 can block Skp2-cyclin A interaction but not p27-cyclin A interaction, whereas a previously identified RxL peptide can block p27-cyclin A interaction but not Skp2-cyclin A interaction. Functionally, Skp2-cyclin A interaction is separable from Skp2’s ability to mediate p27 ubiquitylation. Rather, Skp2-cyclin A interaction serves to directly protect cyclin A/Cdk2 from inhibition by p27 through competitive binding. Finally, we show that disruption of cyclin A binding with point mutations in the cyclin A binding domain of Skp2 compromises the ability of overexpressed Skp2 to counter cell cycle arrest by a p53/p21 mediated cell cycle checkpoint without affecting its ability to cause degradation of cellular p27 and p21. These findings reveal a new functional mechanism of Skp2 and a new regulatory mechanism of cyclin A.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:


Home page
 DiabetesHome page
W.-J. Song, W. E. Schreiber, E. Zhong, F.-F. Liu, B. D. Kornfeld, F. E. Wondisford, and M. A. Hussain
Exendin-4 Stimulation of Cyclin A2 in {beta}-Cell Proliferation
Diabetes, September 1, 2008; 57(9): 2371 - 2381.
[Abstract] [Full Text] [PDF]

Home page
 J. Cell Sci.Home page
H. Wang, D. Sun, P. Ji, J. Mohler, and L. Zhu
An AR-Skp2 pathway for proliferation of androgen-dependent prostate-cancer cells
J. Cell Sci., August 1, 2008; 121(15): 2578 - 2587.
[Abstract] [Full Text] [PDF]

Home page
 Molecular Cancer TherapeuticsHome page
P. Ji, D. Sun, H. Wang, F. Bauzon, and L. Zhu
Disrupting Skp2-cyclin A interaction with a blocking peptide induces selective cancer cell killing
Mol. Cancer Ther., February 1, 2007; 6(2): 684 - 691.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
 All ASBMB Journals   Molecular and Cellular Proteomics 
 Journal of Lipid Research   ASBMB Today 
Copyright © 2006 by the American Society for Biochemistry and Molecular Biology.