Sin3b Interacts with Myc and Decreases Myc Levels [Cell Biology]

June 20th, 2014 by Garcia-Sanz, P., Quintanilla, A., Lafita, M. C., Moreno-Bueno, G., Garcia-Gutierrez, L., Tabor, V., Varela, I., Shiio, Y., Larsson, L.-G., Portillo, F., Leon, J.

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 colocalize and interact in the nuclei of human and rat cells, as assessed by coimmunoprecipitation, immunofluorescence, and proximity ligation assay. The interaction is Max independent. A conserved Myc region (amino acids 186 to 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 cooccupied many sites on the chromatin of human leukemia cells, although the presence of Sin3 was not associated with gene downregulation. In leukemia cells and fibroblasts, Sin3b silencing led to Myc upregulation, whereas Sin3b overexpression induced Myc deacetylation and degradation. 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 the 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.