pRB and p107 have distinct effects when expressed in pRB-deficient tumor cells at physiologically relevant levels

被引:15
作者
Jiang, H [1 ]
Karnezis, AN [1 ]
Tao, MY [1 ]
Guida, PM [1 ]
Zhu, L [1 ]
机构
[1] Albert Einstein Coll Med, Dept Dev & Mol Biol, Bronx, NY 10461 USA
关键词
tumor suppressor; retinoblastoma protein; p107; E2F; growth suppression;
D O I
10.1038/sj.onc.1203722
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
A key difference among the three structurally similar pRB family members is that only pRB is a tumor suppressor. Identification of distinctive functional differences between pRB and p107/p130 therefore holds promise for a better understanding of the tumor suppression mechanisms of pRB, Enigmatically, pRB and p107 have been shown to have indistinguishable growth suppression activities when studied in the pRB-deficient Saos-2 cell system. In this study, we discovered that, when expressed at physiologically relevant levels, pRB and p107 had distinctive effects in causing growth suppression, pRB induced cellular p130 levels while p107 repressed them, p107, but not pRB, blocked cells inside S phase in addition to G1 arrest. In contrast, no qualitative differences were identified in their abilities to repress the expression of a set of suspected pRB/E2F repression target genes. These results indicate that pRB and p107 possess different growth suppression effects, despite the fact that they have similar E2F repression effects.
引用
收藏
页码:3878 / 3887
页数:10
相关论文
共 59 条
[41]   GROWTH SUPPRESSION BY P16(INK4) REQUIRES FUNCTIONAL RETINOBLASTOMA PROTEIN [J].
MEDEMA, RH ;
HERRERA, RE ;
LAM, F ;
WEINBERG, RA .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (14) :6289-6293
[42]   The retinoblastoma gene family: cousins with overlapping interests [J].
Mulligan, G ;
Jacks, T .
TRENDS IN GENETICS, 1998, 14 (06) :223-229
[43]  
Nevins JR, 1998, CELL GROWTH DIFFER, V9, P585
[44]   Skeletal muscle cells lacking the retinoblastoma protein display defects in muscle gene expression and accumulate in S and G(2) phases of the cell cycle [J].
Novitch, BG ;
Mulligan, GJ ;
Jacks, T ;
Lassar, AB .
JOURNAL OF CELL BIOLOGY, 1996, 135 (02) :441-456
[45]   ROLE OF THE UBIQUITIN-PROTEASOME PATHWAY IN REGULATING ABUNDANCE OF THE CYCLIN-DEPENDENT KINASE INHIBITOR P27 [J].
PAGANO, M ;
TAM, SW ;
THEODORAS, AM ;
BEERROMERO, P ;
DELSAL, G ;
CHAU, V ;
YEW, PR ;
DRAETTA, GF ;
ROLFE, M .
SCIENCE, 1995, 269 (5224) :682-685
[46]   IDENTIFICATION OF A GROWTH SUPPRESSION DOMAIN WITHIN THE RETINOBLASTOMA GENE-PRODUCT [J].
QIN, XQ ;
CHITTENDEN, T ;
LIVINGSTON, DM ;
KAELIN, WG .
GENES & DEVELOPMENT, 1992, 6 (06) :953-964
[47]   p107 is a suppressor of retinoblastoma development in pRb-deficient mice [J].
Robanus-Maandag, E ;
Dekker, M ;
van der Valk, M ;
Carrozza, ML ;
Jeanny, JC ;
Dannenberg, JH ;
Berns, A ;
Riele, HT .
GENES & DEVELOPMENT, 1998, 12 (11) :1599-1609
[48]   REVERSAL OF TERMINAL DIFFERENTIATION MEDIATED BY P107 IN RB(-/-) MUSCLE-CELLS [J].
SCHNEIDER, JW ;
GU, W ;
ZHU, L ;
MAHDAVI, V ;
NADALGINARD, B .
SCIENCE, 1994, 264 (5164) :1467-1471
[49]   Stable binding to E2F is not required for the retinoblastoma protein to activate transcription, promote differentiation, and suppress tumor cell growth [J].
Sellers, WR ;
Novitch, BG ;
Miyake, S ;
Heith, A ;
Otterson, GA ;
Kaye, FJ ;
Lassar, AB ;
Kaelin, WG .
GENES & DEVELOPMENT, 1998, 12 (01) :95-106
[50]  
Smith EJ, 1998, CELL GROWTH DIFFER, V9, P297