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Inhibition of oncogenic transformation by mammalian Lin‐9, a pRB‐associated protein
Author(s) -
Gagrica Sladjana,
Hauser Stefanie,
Kolfschoten Ingrid,
Osterloh Lisa,
Agami Reuven,
Gaubatz Stefan
Publication year - 2004
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7600470
Subject(s) - biology , transformation (genetics) , retinoblastoma protein , microbiology and biotechnology , genetics , cancer research , cell cycle , gene
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.