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. © 1994. |
Keywords: |
sequence analysis; genetics; nonhuman; molecular genetics; animal cell; mouse; animal; metabolism; mice; cell cycle; protein kinases; transforming growth factor beta; cell line; enzyme activation; drug effect; phosphorylation; animalia; molecular cloning; cloning, molecular; amino acid sequence; molecular sequence data; messenger rna; rna, messenger; sequence alignment; nucleotide sequence; organ specificity; antibody specificity; cycline; sequence homology; cyclins; isolation and purification; protein kinase; enzyme purification; cell cycle g1 phase; g1 phase; fungal protein; mink; contact inhibition; fungal proteins; cell contact; microtubule-associated proteins; microtubule associated protein; cdkn1b; human; priority journal; article; support, non-u.s. gov't; support, u.s. gov't, p.h.s.; mustela vison; microtubule associated proteins; cdk2 protein; p34psk j3 kinase; p34psk-j3 kinase
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