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Cancer Res. 2006 Feb 1;66(3):1289-93.

The c-myc gene is a direct target of mammalian SWI/SNF-related complexes during differentiation-associated cell cycle arrest.

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1
Fels Institute for Cancer Research and Molecular Biology, Temple University School of Medicine, Philadelphia, PA 19140, USA.

Abstract

The activity of mammalian SWI/SNF-related chromatin remodeling complexes is crucial for differentiation, development, and tumor suppression. Cell cycle-regulating activities dependent on the complexes include induction of the p21(WAF1/CIP1) kinase inhibitor and repression of E2F-responsive promoters. These responses are linked through effects on pRb phosphorylation, but the direct role of the SWI/SNF-related complexes in their regulation is not fully understood. Results presented here reveal that the complexes are required for regulation of a distinct pathway of proliferation control involving repression of c-myc expression in differentiating cells. This involves direct promoter targeting of the c-myc gene by the complexes. Induction of p21(WAF1/CIP1) is specifically dependent on prior repression of c-myc, but repression of E2F-responsive genes is dissociable from the regulation of c-myc and p21(WAF1/CIP1).

PMID:
16452181
DOI:
10.1158/0008-5472.CAN-05-3427
[Indexed for MEDLINE]
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