title: A role of helix 12 of the vitamin D receptor in SMRT corepressor interaction.
abstract: To repress gene transcription, the unliganded nuclear receptor (NR) recruits the N-CoR and SMRT corepressors via its direct association with the conserved motif within bipartite NR-interaction domains (IDs) of corepressors. We recently reported that SMRT is directly involved in the VDR-mediated repression via an ID1-specific interaction with the VDR. Here we show that removal of helix 12 from VDR (VDRDeltaAF2) converts it to a more potent repressor through additional interaction between the VDR and SMRT-ID2 in yeast and mammalian systems. These data suggest that the VDR helix 12 actively regulates the ID1 preference of the VDR by inhibiting ID2-VDR association. Using the one- plus two-hybrid system, we identified specific residues within the extended helix motif of SMRT-ID2 that are required for VDRDeltaAF2 binding. Analyses of these mutants also revealed the specific residues of SMRT-ID2 generally required for optimal NR binding as well as those involved in preferential interaction with specific NRs.
authors.affiliation: Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju, South Korea.
authors.forename: Ji Young
authors.initials: JY
authors.lastname: Kim
authors.forename: You Lee
authors.initials: YL
authors.lastname: Son
authors.forename: Young Chul
authors.initials: YC
authors.lastname: Lee
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D056985:Nuclear Receptor Co-Repressor 2; D017433:Protein Structure, Secondary; D017434:Protein Structure, Tertiary; D018167:Receptors, Calcitriol / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D017384:Sequence Deletion; D014158:Transcription, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D018167:Receptors, Calcitriol; D012097:Repressor Proteins