title: Diverse signaling pathways modulate nuclear receptor recruitment of N-CoR and SMRT complexes.
abstract: Several lines of evidence indicate that the nuclear receptor corepressor (N-CoR) complex imposes ligand dependence on transcriptional activation by the retinoic acid receptor and mediates the inhibitory effects of estrogen receptor antagonists, such as tamoxifen, suppressing a constitutive N-terminal, Creb-binding protein/coactivator complex-dependent activation domain. Functional interactions between specific receptors and N-CoR or SMRT corepressor complexes are regulated, positively or negatively, by diverse signal transduction pathways. Decreased levels of N-CoR correlate with the acquisition of tamoxifen resistance in a mouse model system for human breast cancer. Our data suggest that N-CoR- and SMRT-containing complexes act as rate-limiting components in the actions of specific nuclear receptors, and that their actions are regulated by multiple signal transduction pathways.
authors.affiliation: Howard Hughes Medical Institute, Department and School of Medicine, University of California at San Diego, La Jolla, CA 92093-0648, USA.
authors.forename: R M
authors.initials: RM
authors.lastname: Lavinsky
authors.forename: K
authors.initials: K
authors.lastname: Jepsen
authors.forename: T
authors.initials: T
authors.lastname: Heinzel
authors.forename: J
authors.initials: J
authors.lastname: Torchia
authors.forename: T M
authors.initials: TM
authors.lastname: Mullen
authors.forename: R
authors.initials: R
authors.lastname: Schiff
authors.forename: A L
authors.initials: AL
authors.lastname: Del-Rio
authors.forename: M
authors.initials: M
authors.lastname: Ricote
authors.forename: S
authors.initials: S
authors.lastname: Ngo
authors.forename: J
authors.initials: J
authors.lastname: Gemsch
authors.forename: S G
authors.initials: SG
authors.lastname: Hilsenbeck
authors.forename: C K
authors.initials: CK
authors.lastname: Osborne
authors.forename: C K
authors.initials: CK
authors.lastname: Glass
authors.forename: M G
authors.initials: MG
authors.lastname: Rosenfeld
authors.forename: D W
authors.initials: DW
authors.lastname: Rose
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004195:Disease Models, Animal; D004351:Drug Resistance; D004965:Estrogen Antagonists / Q000494:pharmacology*; D005786:Gene Expression Regulation; D017930:Genes, Reporter; D006801:Humans; D051379:Mice; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011485:Protein Binding; D011494:Protein Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism*; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism*; D015398:Signal Transduction; D013629:Tamoxifen / Q000494:pharmacology*
chemical_list: D004268:DNA-Binding Proteins; D004965:Estrogen Antagonists; C539127:NCOR1 protein, human; C539130:NCOR2 protein, human; C539128:Ncor1 protein, mouse; C539131:Ncor2 protein, mouse; D009687:Nuclear Proteins; D056971:Nuclear Receptor Co-Repressor 1; D056985:Nuclear Receptor Co-Repressor 2; D011960:Receptors, Estrogen; D018168:Receptors, Retinoic Acid; D012097:Repressor Proteins; D013629:Tamoxifen; D011494:Protein Kinases