ras transformation is associated with decreased expression of the brm/SNF2alpha ATPase from the mammalian SWI-SNF complex.
The brm and BRG-1 proteins are mutually exclusive subunits of the mammalian SWI-SNF complex. Within this complex, they provide the ATPase activity necessary for transcriptional regulation by nucleosome disruption. Both proteins were recently found to interact with the p105Rb tumor suppressor gene product, suggesting a role for the mammalian SWI-SNF complex in the control of cell growth. We show here that the expression of brm, but not BRG-1, is negatively regulated by mitogenic stimulation, and that growth arrest of mouse fibroblasts leads to increased accumulation of the brm protein. The expression of this protein is also down-regulated upon transformation by the ras oncogene. Re-introduction of brm into ras transformed cells leads to partial reversion of the transformed phenotype by a mechanism that depends on the ATPase domain of the protein. Our data suggest that increased levels of brm protein favour the withdrawal of the cell from the cycle whereas decreased expression of the brm gene may facilitate cellular transformation by various oncogenes.
Muchardt
C
C
Unité des Virus Oncogènes, URA1644 du CNRS, Département des Biotechnologies, Institut Pasteur, 25, rue du Docteur Roux, 75724 Paris Cedex 15, France.
Bourachot
B
B
Reyes
J C
JC
Yaniv
M
M
D016475:3T3 Cells; D000251:Adenosine Triphosphatases / Q000235:genetics*; D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015536:Down-Regulation; D005786:Gene Expression Regulation; D011905:Genes, ras; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008934:Mitogens / Q000494:pharmacology; D009857:Oncogenes; D010641:Phenotype; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*
D008934:Mitogens; C084011:SMARCA2 protein, human; C499503:Smarca2 protein, mouse; D014157:Transcription Factors; D000251:Adenosine Triphosphatases