Inhibition of oncogenic transformation by mammalian Lin-9, a pRB-associated protein

被引:53
|
作者
Gagrica, S
Hauser, S
Kolfschoten, I
Osterloh, L
Agami, R
Gaubatz, S
机构
[1] Univ Marburg, Inst Mol Biol & tumor Res, D-35037 Marburg, Germany
[2] Netherlands Canc Inst, Div Tumor Biol, Amsterdam, Netherlands
来源
EMBO JOURNAL | 2004年 / 23卷 / 23期
关键词
differentiation; hLin-9; oncogenic transformation; retinoblastoma; tumor suppressor;
D O I
10.1038/sj.emboj.7600470
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
Genetic studies in Caenorhabditis elegans identified lin-9 to function together with the retinoblastoma homologue lin-35 in vulva differentiation. We have now identified a human homologue of Lin-9 (hLin-9) and provide evidence about its function in the mammalian pRB pathway. hLin-9 binds to pRB and cooperates with pRB in flat cell formation in Saos-2 cells. In addition, hLin-9 synergized with pRB and Cbfal to transactivate an osteoblast-specific reporter gene. In contrast, hLin-9 was not involved in pRB-mediated inhibition of cell cycle progression or repression of E2F-dependent transactivation. Consistent with these data, hLin-9 was able to associate with partially penetrant pRB mutants that do not bind to E2F, but retain the ability to activate transcription and to promote differentiation. hLin-9 can also inhibit oncogenic transformation, dependent on the presence of a functional pRB protein. RNAi-mediated knockdown of Lin-9 can substitute for the loss of pRB in transformation of human primary fibroblasts. These data suggest that hLin-9 has tumor-suppressing activities and that the ability of hLin-9 to inhibit transformation is mediated through its association with pRB.
引用
收藏
页码:4627 / 4638
页数:12
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