title: 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.
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain, the Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Facultad de Medicina, Universidad Autónoma de Madrid, 28046 Madrid, Spain, the Fundación M. D. Anderson Internacional, Madrid, Spain.
authors.forename: Pablo
authors.initials: P
authors.lastname: Garcia-Sanz
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain.
authors.forename: Andrea
authors.initials: A
authors.lastname: Quintanilla
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain.
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Lafita
authors.affiliation: the Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Facultad de Medicina, Universidad Autónoma de Madrid, 28046 Madrid, Spain, the Fundación M. D. Anderson Internacional, Madrid, Spain.
authors.forename: Gema
authors.initials: G
authors.lastname: Moreno-Bueno
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain.
authors.forename: Lucia
authors.initials: L
authors.lastname: García-Gutierrez
authors.affiliation: the Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm SE-17177, Sweden, and.
authors.forename: Vedrana
authors.initials: V
authors.lastname: Tabor
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Varela
authors.affiliation: the Greehey Children's Cancer Research Institute, The University of Texas Health Science Center, San Antonio, Texas 78229-3900.
authors.forename: Yuzuru
authors.initials: Y
authors.lastname: Shiio
authors.affiliation: the Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm SE-17177, Sweden, and.
authors.forename: Lars-Gunnar
authors.initials: LG
authors.lastname: Larsson
authors.affiliation: the Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas, Instituto de Investigación Hospital Universitario La Paz (IdiPaz), Facultad de Medicina, Universidad Autónoma de Madrid, 28046 Madrid, Spain, fportillo@iib.uam.es.
authors.forename: Francisco
authors.initials: F
authors.lastname: Portillo
authors.affiliation: From the Instituto de Biomedicina y Biotecnología de Cantabria (IBBTEC), Consejo Superior de Investigaciones Científicas, Universidad de Cantabria, Sociedad para el Desarrollo de Cantabria and the Departamento de Biología Molecular, Universidad de Cantabria, Santander 39011, Spain, leonj@unican.es.
authors.forename: Javier
authors.initials: J
authors.lastname: Leon
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D016259:Genes, myc; D057809:HEK293 Cells; D056284:Histone Deacetylase 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D020014:K562 Cells; D008875:Middle Aged; D008954:Models, Biological; D054730:Protein Interaction Domains and Motifs; D059748:Proteolysis; D016271:Proto-Oncogene Proteins c-myc / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D012097:Repressor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D020798:Two-Hybrid System Techniques
chemical_list: C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D012097:Repressor Proteins; C492042:SIN3B protein, human; C110550:HDAC1 protein, human; D056284:Histone Deacetylase 1
keywords: Breast Cancer; Gene Expression; Histone Deacetylase (HDAC); Myc (c-Myc); Sin3b; Transcription