JCB logo
Accuri Cytometers
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 25 June 2001. doi:10.1083/jcb.153.7.1381
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 247K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Carrano, A. C.
Right arrow Articles by Pagano, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Carrano, A. C.
Right arrow Articles by Pagano, M.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/2001//1381 $5.00
The Journal of Cell Biology, Volume 153, Number 7, , 2001 1381-1390

Original Article

Role of the F-Box Protein Skp2 in Adhesion-Dependent Cell Cycle Progression



Andrea C. Carranoa and Michele Paganoa

a Department of Pathology and Kaplan Comprehensive Cancer Center, MSB 548, New York University School of Medicine, New York, New York 10016
New York University School of Medicine, Kaplan Comprehensive Cancer Center, Dept. of Pathology, MSB 548, 550 First Ave., New York, NY 10016.(212) 263-8211(212) 263-5332

paganm02{at}med.nyu.edu

Cell adhesion to the extracellular matrix (ECM) is a requirement for proliferation that is typically lost in malignant cells. In the absence of adhesion, nontransformed cells arrest in G1 with increased levels of the cyclin-dependent kinase inhibitor p27. We have reported previously that the degradation of p27 requires its phosphorylation on Thr-187 and is mediated by Skp2, an F-box protein that associates with Skp1, Cul1, and Roc1/Rbx1 to form the SCFSkp2 ubiquitin ligase complex. Here, we show that the accumulation of Skp2 protein is dependent on both cell adhesion and growth factors but that the induction of Skp2 mRNA is exclusively dependent on cell adhesion to the ECM. Conversely, the expression of the other three subunits of the SCFSkp2 complex is independent of cell anchorage. Phosphorylation of p27 on Thr-187 is also not affected significantly by the loss of cell adhesion, demonstrating that increased p27 stability is not dependent on p27 dephosphorylation. Significantly, ectopic expression of Skp2 in nonadherent G1 cells resulted in p27 downregulation, entry into S phase, and cell division. The ability to induce adhesion-independent cell cycle progression was potentiated by coexpressing Skp2 with cyclin D1 but not with cyclin E, indicating that Skp2 and cyclin D1 cooperate to rescue proliferation in suspension cells. Our study shows that Skp2 is a key target of ECM signaling that controls cell proliferation.

Key Words: F-box protein • SCF • Skp2 • p27 • cell adhesion control

© 2001 The Rockefeller University Press

Abbreviations used in this paper: Act D, actinomycin D; Adh, adherent; Cdk, cyclin-dependent kinase; Chx, cycloheximide; ECM, extracellular matrix; Fbp, F-box protein; Mab, mouse monoclonal antibody; PDL, population doubling; SCF, Skp1, Cul1, and Fbp complex; Skp, S phase kinase-associated protein; Susp, suspension.


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 Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?




  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents