A role of helix 12 of the vitamin D receptor in SMRT corepressor interaction
- Hormone Research Center, School of Biological Sciences and Technology, Chonnam National University, 300 Yongbong-dong, Buk-gu, Gwangju 500-757 (Korea, Republic of)
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 (VDR{delta}AF2) 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 VDR{delta}AF2 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.
- OSTI ID:
- 21255885
- Journal Information:
- Biochemical and Biophysical Research Communications, Vol. 379, Issue 3; Other Information: DOI: 10.1016/j.bbrc.2008.12.156; PII: S0006-291X(08)02553-9; Copyright (c) 2008 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); ISSN 0006-291X
- Country of Publication:
- United States
- Language:
- English
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