BRCA1 transactivates the cyclin-dependent kinase inhibitor p27Kip1

被引:49
作者
Williamson, EA
Dadmanesh, F
Koeffler, HP
机构
[1] Univ Calif Los Angeles, Sch Med, Dept Med, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
[2] Univ Calif Los Angeles, Sch Med, Dept Anat Pathol, Cedars Sinai Med Ctr, Los Angeles, CA 90048 USA
关键词
BRCA1; p27(Kip1); transcriptional regulation;
D O I
10.1038/sj.onc.1205461
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
The p27(Kip1) is a member of the universal cyclin-dependent kinase inhibitor family. Previously, immunochemical analysis of a series of breast cancer cell lines demonstrated a correlation between the expression of P27(Kip1) and the breast cancer susceptibility gene BRCA1. BRCA1 has a number of activities including DNA repair, growth inhibition and as a transcription factor. Here we demonstrate that BRCA1 transactivates expression of p27(Kip1). This transactivation is dependent on the presence of a functional C-terminal transactivation domain. Promoter-deletion analysis identified the presence of a putative BRCA1-responsive element located at position -615 to -511 of the p27(Kip1) promoter. These results suggest that the transcriptional regulation of p27(Kip1) by BRCA1 may be a mechanism for BRCA1- induced growth inhibition.
引用
收藏
页码:3199 / 3206
页数:8
相关论文
共 39 条
[21]   Functional motifs [J].
Koonin, EV ;
Altschul, SF ;
Bork, P .
NATURE GENETICS, 1996, 13 (03) :266-268
[22]   Characterization of the murine cyclin-dependent kinase inhibitor gene p27(Kip1) [J].
Kwon, TK ;
Nagel, JE ;
Buchholz, MA ;
Nordin, AA .
GENE, 1996, 180 (1-2) :113-120
[23]  
Masciullo V, 1999, CANCER RES, V59, P3790
[24]   AFX-like Forkhead transcription factors mediate cell-cycle regulation by Ras and PKB through p27kip1 [J].
Medema, RH ;
Kops, GJPL ;
Bos, JL ;
Burgering, BMT .
NATURE, 2000, 404 (6779) :782-787
[25]   Molecular cloning and characterization of the human p27(Kip1) gene promoter [J].
Minami, S ;
OhtaniFujita, N ;
Igata, E ;
Tamaki, T ;
Sakai, T .
FEBS LETTERS, 1997, 411 (01) :1-6
[26]   BRCA1 expression status in relation to DNA methylation of the BRCA1 promoter region in sporadic breast cancers [J].
Niwa, Y ;
Oyama, T ;
Nakajima, T .
JAPANESE JOURNAL OF CANCER RESEARCH, 2000, 91 (05) :519-526
[27]   Expression of p27(Kip1) in osteoblast-like cells during differentiation with parathyroid hormone [J].
Onishi, T ;
Hruska, K .
ENDOCRINOLOGY, 1997, 138 (05) :1995-2004
[28]   BRCA1 regulates p53-dependent gene expression [J].
Ouchi, T ;
Monteiro, ANA ;
August, A ;
Aaronson, SA ;
Hanafusa, H .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (05) :2302-2306
[29]   P27(KIP1), A CYCLIN-CDK INHIBITOR, LINKS TRANSFORMING GROWTH-FACTOR-BETA AND CONTACT INHIBITION TO CELL-CYCLE ARREST [J].
POLYAK, K ;
KATO, JY ;
SOLOMON, MJ ;
SHERR, CJ ;
MASSAGUE, J ;
ROBERTS, JM ;
KOFF, A .
GENES & DEVELOPMENT, 1994, 8 (01) :9-22
[30]   Association of BRCA1 with Rad51 in mitotic and meiotic cells [J].
Scully, R ;
Chen, JJ ;
Plug, A ;
Xiao, YH ;
Weaver, D ;
Feunteun, J ;
Ashley, T ;
Livingston, DM .
CELL, 1997, 88 (02) :265-275