Cell
Volume 78, Issue 1, 15 July 1994, Pages 59-66
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Cloning of p27Kip1, a cyclin-dependent kinase inhibitor and a potential mediator of extracellular antimitogenic signals

https://doi.org/10.1016/0092-8674(94)90572-XGet rights and content

Abstract

We cloned P27Kip1, a cyclin-dependent kinase inhibitor implicated in G1 phase arrest by TGFβ and cell-cell contact. p27Kip1 associates with cyclin E-Cdk2 complexes in vivo and in vitro, prevents their activation, and inhibits previously activated complexes, and p27Kip1 overexpression obstructs cell entry into S phase. p27Kip1 potently inhibits Rb phosphorylation by cyclin E-Cdk2, cyclin A-Cdk2, and cyclin D2-Cdk4. p27Kip1 is highly conserved and broadly expressed in human tissues, and its mRNA levels are similar in proliferating and quiescent cells. p27Kip1 has a region of sequence similarity to p21Cip1/WAF1, the Cdk inhibitor whose transcription is stimulated by p53. A p27Kip1 peptide corresponding to this region retains Cdk inhibitory activity. We suggest that cell contact, TGFβ, and p53 all restrain cell proliferation through related Cdk inhibitors.

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