RB regulates the stability and the apoptotic function of p53 via MDM2

被引:226
作者
Hsieh, JK
Chan, FSG
O'Connor, DJ
Mittnacht, S
Zhong, S
Lu, X
机构
[1] Imperial Coll Sch Med, Ludwig Inst Canc Res, London W2 1PG, England
[2] Inst Canc Res, London SW3 6JB, England
关键词
D O I
10.1016/S1097-2765(00)80309-3
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 binding of RE to MDM2 is shown to be essential for RE to overcome both the antiapoptotic function of MDM2 and the MDMP-dependent degradation of p53. The RB-MDM2 interaction does not prevent MDM2 from inhibiting p53-dependent transcription, but the RB-MDM2 complex still binds to p53. Since RE specifically rescues the apoptotic function but not the transcriptional activity of p53 from negative regulation by MDM2, transactivation by wild-type p53 is not required for the apoptotic function of p53. However, an RB-MDM2-p53 trimeric complex is active in p53-mediated transrepression. These data link directly the function of two tumor suppressor proteins and demonstrate a novel role of RE in regulating the apoptotic function of p53.
引用
收藏
页码:181 / 193
页数:13
相关论文
共 40 条
[1]  
[Anonymous], 1988, Antibodies: A Laboratory Manual
[2]   Deletion of RB exons 24 and 25 causes low-penetrance retinoblastoma [J].
Bremner, R ;
Du, DC ;
ConnollyWilson, MJ ;
Bridge, P ;
Ahmad, KF ;
Mostachfi, H ;
Rushlow, D ;
Dunn, JM ;
Gallie, BL .
AMERICAN JOURNAL OF HUMAN GENETICS, 1997, 61 (03) :556-570
[3]   REGULATION OF TRANSCRIPTION FUNCTIONS OF THE P53 TUMOR-SUPPRESSOR BY THE MDM-2 ONCOGENE [J].
CHEN, JD ;
LIN, JY ;
LEVINE, AJ .
MOLECULAR MEDICINE, 1995, 1 (02) :142-152
[4]   pRB phosphorylation mutants reveal role of pRB in regulating S phase completion by a mechanism independent of E2F [J].
Chew, YP ;
Ellis, M ;
Wilkie, S ;
Mittnacht, S .
ONCOGENE, 1998, 17 (17) :2177-2186
[5]  
Chow KNB, 1996, MOL CELL BIOL, V16, P7173
[6]  
CordonCardo C, 1997, CANCER RES, V57, P1217
[7]   TRANSCRIPTIONAL ACTIVATION BY P53 CORRELATES WITH SUPPRESSION OF GROWTH BUT NOT TRANSFORMATION [J].
CROOK, T ;
MARSTON, NJ ;
SARA, EA ;
VOUSDEN, KH .
CELL, 1994, 79 (05) :817-827
[8]   High level expression of p27(kip1) and cyclin D1 in some human breast cancer cells: Inverse correlation between the expression of p27(kip1) and degree of malignancy in human breast and colorectal cancers [J].
Fredersdorf, S ;
Burns, J ;
Milne, AM ;
Packham, G ;
Fallis, L ;
Gillett, CE ;
Royds, JA ;
Peston, D ;
Hall, PA ;
Hanby, AM ;
Barnes, DM ;
Shousha, S ;
OHare, MJ ;
Lu, X .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (12) :6380-6385
[9]  
FUCHS B, 1995, ONCOGENE, V10, P789
[10]   Cell type-specific inhibition of p53-mediated apoptosis by mdm2 [J].
Haupt, Y ;
Barak, Y ;
Oren, M .
EMBO JOURNAL, 1996, 15 (07) :1596-1606