CLONING AND CHARACTERIZATION OF RAT P27(KIP1), A CYCLIN-DEPENDENT KINASE INHIBITOR

Cyclin-dependent kinase (Cdk) inhibitors play significant roles in the cell cycle control of various biological phenomena. To characterize t he role of Cdk inhibitors in rat cells, we isolated a cDNA encoding ra t p27(Kip1) a 27-kDa Cdk inhibitor. The 1.04-kb cDNA of rat p27 contai ned an open reading frame of 197 amino acids that shared high homology with mammalian p27 and significant homology with mammalian p21(Cip1) and p57(Kip2). p27 mRNA was detected in most rat tissues and cell line s. The levels of p27 protein expression were similar in rat cell lines transformed by E1A and in normal cells. Rat p27 was able to interact with Cdk 2/4 and cyclin A/D in rat cells, but the amounts of rat p27 i n Cdk2 complexes were different between transformed cells and normal c ells. Thus, the formation of stable complexes of rat p27 may be modula ted by E1A. Rat p27 protein could inhibit the increased Cdk2-associate d kinase activity in transformed rat cells. (C) 1997 Elsevier Science B.V.