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J Biol Chem, Vol. 274, Issue 8, 4485-4488, February 19, 1999
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From the The mechanism by which the viral
oncogene ski (v-ski) transforms chicken embryo
fibroblasts is currently unknown. Recently, the c-ski gene
product (c-Ski) was found to bind to N-CoR (nuclear hormone receptor
co-repressor), an element implicated in transcriptional repression
mediated by multiple transcriptional repressors including the nuclear
hormone receptors and Mad. c-Ski is required for transcriptional repression mediated by Mad involved in negative regulation of cellular
proliferation. v-Ski abrogates Mad-induced transcriptional repression
in a dominant negative fashion. Here we report that v-Ski also inhibits
transcriptional repression mediated by Rb, another tumor suppressor
gene product. Rb forms a complex with c-Ski, Sin3A, and
histone deacetylase (HDAC) via direct binding to c-Ski and
HDAC. c-Ski is required for the transcriptional repression mediated by
Rb. These results suggest that inhibition of Rb activity contributes,
at least partly, to transformation by v-Ski.
Laboratory of Molecular Genetics,
Tsukuba Life Science Center, RIKEN, 3-1-1 Koyadai, Tsukuba, Ibaraki
305-0074, Japan, the § Institute of Medical Sciences,
University of Tsukuba, 1-1-1 Tennoudai, Tsukuba, Ibaraki 305-0006, Japan, the ** National Institute of Bioscience and Human Technology,
Agency of Industrial Science and Technology, 1-1 Higashi, Tsukuba,
Ibaraki 305-0046, Japan, the Chugai
Research Institute for Molecular Medicine, 153-2 Nagai, Niihari,
Ibaraki 300-4101, Japan, the §§ Iatron
Laboratories Inc., 1460-6 Mitodai, Tako, Katori, Chiba 289-2247, Japan,
and the ¶ CREST (Core Research for Evolutional Science and
Technology), JST
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