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Sin3b interacts with Myc and decreases Myc levels

Abstract: Myc expression is deregulated in many human cancers. A yeast two-hybrid screen has revealed that the transcriptional repressor Sin3b interacts with Myc protein. Endogenous Myc and Sin3b co-localize and interact in the nuclei of human and rat cells, as assessed by co-immunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max-independent. A conserved Myc region (amino acids 186-203) is required for the interaction with Sin3 proteins. Histone deacetylase 1 is recruited to Myc-Sin3b complexes, and its deacetylase activity is required for the effects of Sin3b on Myc. Myc and Sin3a/b co-occupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene down-regulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc up-regulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. An analysis of Sin3b expression in breast tumors revealed an association between low Sin3b expression and disease progression. The data suggest that Sin3b decreases Myc protein levels upon Myc deacetylation. As Sin3b is also required for transcriptional repression by Mxd-Max complexes, our results suggest that, at least in some cell types, Sin3b limits Myc activity through two complementary activities: Mxd-dependent gene repression and reduction of Myc levels.

 Fuente: J Biol Chem. 2014 Aug 8;289(32):22221-36

Editorial: American Society for Biochemistry and Molecular Biology Inc.

 Fecha de publicación: 08/08/2014

Nº de páginas: 16

Tipo de publicación: Artículo de Revista

 DOI: 10.1074/jbc.M113.538744

ISSN: 0021-9258,1083-351X

Proyecto español: ReCaRe S2010/BMD-2303, RETIC/RD012/0036/0033, SAF11-23796, SAF2010-20175,

Autores/as

PABLO GARCIA SANZ

ANDREA QUINTANILLA CAVIA

MARIA DEL CARMEN LAFITA NAVARRO

MORENO BUENO, GEMA

LUCIA GARCIA GUTIERREZ

TABOR, VEDRANA

SHIIO, YUZURU

LARSSON, LARS-GUNNAR

PORTILLO, FRANCISCO