CLONING OF P27(KIP1), A CYCLIN-DEPENDENT KINASE INHIBITOR AND A POTENTIAL MEDIATOR OF EXTRACELLULAR ANTIMITOGENIC SIGNALS

被引：2069
作者：
POLYAK, K
LEE, MH
ERDJUMENTBROMAGE, H
KOFF, A
ROBERTS, JM
TEMPST, P
MASSAGUE, J
机构：
[1] MEM SLOAN KETTERING CANC CTR,PROGRAM MOLEC BIOL,NEW YORK,NY 10021
[2] FRED HUTCHINSON CANC RES CTR,DEPT BASIC SCI,SEATTLE,WA 98104
来源：
CELL | 1994年 / 78卷 / 01期
基金：
美国国家卫生研究院;
关键词：
D O I：
10.1016/0092-8674(94)90572-X
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
We cloned p27(Kip1), a cyclin-dependent kinase inhibitor implicated in G1 phase arrest by TGF beta and cell-cell contact. p27(Kip1) associates with cyclin E-Cdk2 complexes in vivo and in vitro, prevents their activation, and inhibits previously activated complexes, and p27(Kip1) overexpression obstructs cell entry into S phase. p27(Kip1) potently inhibits Rb phosphorylation by cyclin E-Cdk2, cyclin A-Cdk2, and cyclin D2-Cdk4. p27(Kip1) is highly conserved and broadly expressed in human tissues, and its mRNA levels are similar in proliferating and quiescent cells. p27(Kip1) has a region of sequence similarity to p21(Cip1/WAF1), the Cdk inhibitor whose transcription is stimulated by p53. A p27(Kip1) peptide corresponding to this region retains Cdk inhibitory activity. We suggest that cell contact, TGF beta, and p53 all restrain cell proliferation through related Cdk inhibitors.
引用
收藏
页码：59 / 66
页数：8
相关论文
共 40 条
[1]   IDENTIFICATION OF HUMAN ACTIVIN AND TGF-BETA TYPE-I RECEPTORS THAT FORM HETEROMERIC KINASE COMPLEXES WITH TYPE-II RECEPTORS [J].
ATTISANO, L ;
CARCAMO, J ;
VENTURA, F ;
WEIS, FMB ;
MASSAGUE, J ;
WRANA, JL .
CELL, 1993, 75 (04) :671-680
[2]   IDENTIFICATION OF A GENE NECESSARY FOR CELL-CYCLE ARREST BY A NEGATIVE GROWTH-FACTOR OF YEAST - FAR1 IS AN INHIBITOR OF A G1 CYCLIN, CLN2 [J].
CHANG, F ;
HERSKOWITZ, I .
CELL, 1990, 63 (05) :999-1011
[3]  
COCKS BG, 1992, J BIOL CHEM, V267, P12307
[4]   CRYSTAL-STRUCTURE OF CYCLIN-DEPENDENT KINASE-2 [J].
DEBONDT, HL ;
ROSENBLATT, J ;
JANCARIK, J ;
JONES, HD ;
MORGAN, DO ;
KIM, SH .
NATURE, 1993, 363 (6430) :595-602
[5]   ACTIVATION OF HUMAN CYCLIN-DEPENDENT KINASES INVITRO [J].
DESAI, D ;
GU, Y ;
MORGAN, DO .
MOLECULAR BIOLOGY OF THE CELL, 1992, 3 (05) :571-582
[6]   NUCLEAR TARGETING SEQUENCES - A CONSENSUS [J].
DINGWALL, C ;
LASKEY, RA .
TRENDS IN BIOCHEMICAL SCIENCES, 1991, 16 (12) :478-481
[7]   P53-DEPENDENT INHIBITION OF CYCLIN-DEPENDENT KINASE-ACTIVITIES IN HUMAN FIBROBLASTS DURING RADIATION-INDUCED G1 ARREST [J].
DULIC, V ;
KAUFMANN, WK ;
WILSON, SJ ;
TLSTY, TD ;
LEES, E ;
HARPER, JW ;
ELLEDGE, SJ ;
REED, SI .
CELL, 1994, 76 (06) :1013-1023
[8]  
ELDEIRY WS, 1994, CANCER RES, V54, P1169
[9]   WAF1, A POTENTIAL MEDIATOR OF P53 TUMOR SUPPRESSION [J].
ELDEIRY, WS ;
TOKINO, T ;
VELCULESCU, VE ;
LEVY, DB ;
PARSONS, R ;
TRENT, JM ;
LIN, D ;
MERCER, WE ;
KINZLER, KW ;
VOGELSTEIN, B .
CELL, 1993, 75 (04) :817-825
[10]  
ELICONE C, 1994, IN PRESS J CHROMATOG
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