RGD Reference Report - Role of the F-box protein Skp2 in adhesion-dependent cell cycle progression. - Rat Genome Database

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Role of the F-box protein Skp2 in adhesion-dependent cell cycle progression.

Authors: Carrano, AC  Pagano, M 
Citation: Carrano AC and Pagano M, J Cell Biol. 2001 Jun 25;153(7):1381-90.
RGD ID: 2315071
Pubmed: PMID:11425869   (View Abstract at PubMed)
PMCID: PMC2150734   (View Article at PubMed Central)

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 SCF(Skp2) 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 SCF(Skp2) 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.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to cell-matrix adhesion  IEP 2315071 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Skp2  (S-phase kinase associated protein 2)


Additional Information