A role of helix 12 of the vitamin D receptor in SMRT corepressor interaction.
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.
Kim
Ji Young
JY
Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju, South Korea.
Son
You Lee
YL
Lee
Young Chul
YC
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
D004268:DNA-Binding Proteins; C539130:NCOR2 protein, human; C539131:Ncor2 protein, mouse; D056985:Nuclear Receptor Co-Repressor 2; D018167:Receptors, Calcitriol; D012097:Repressor Proteins