PMID- 11259580
OWN - NLM
STAT- MEDLINE
DCOM- 20010412
LR  - 20240407
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 21
IP  - 7
DP  - 2001 Apr
TI  - PSF is a novel corepressor that mediates its effect through Sin3A and the DNA 
      binding domain of nuclear hormone receptors.
PG  - 2298-311
AB  - Members of the type II nuclear hormone receptor subfamily (e.g., thyroid hormone 
      receptors [TRs], retinoic acid receptors, retinoid X receptors [RXRs], vitamin D 
      receptor, and the peroxisome proliferator-activated receptors) bind to their 
      response sequences with or without ligand. In the absence of ligand, these 
      DNA-bound receptors mediate different degrees of repression or silencing of gene 
      expression which is thought to result from the association of their ligand 
      binding domains (LBDs) with corepressors. Two related corepressors, N-CoR and 
      SMRT, interact to various degrees with the LBDs of these type II receptors in the 
      absence of their cognate ligands. N-CoR and SMRT have been proposed to act by 
      recruiting class I histone deacetylases (HDAC I) through an association with 
      Sin3, although they have also been shown to recruit class II HDACs through a 
      Sin3-independent mechanism. In this study, we used a biochemical approach to 
      identify novel nuclear factors that interact with unliganded full-length TR and 
      RXR. We found that the DNA binding domains (DBDs) of TR and RXR associate with 
      two proteins which we identified as PSF (polypyrimidine tract-binding 
      protein-associated splicing factor) and NonO/p54(nrb). Our studies indicate that 
      PSF is a novel repressor which interacts with Sin3A and mediates silencing 
      through the recruitment of HDACs to the receptor DBD. In vivo studies with TR 
      showed that although N-CoR fully dissociates in the presence of ligand, the 
      levels of TR-bound PSF and Sin3A appear to remain unchanged, indicating that 
      Sin3A can be recruited to the receptor independent of N-CoR or SMRT. RXR was not 
      detected to bind N-CoR although it bound PSF and Sin3A as effectively as TR, and 
      this association with RXR did not change with ligand. Our studies point to a 
      novel PSF/Sin3-mediated pathway for nuclear hormone receptors, and possibly other 
      transcription factors, which may fine-tune the transcriptional response as well 
      as play an important role in mediating the repressive effects of those type II 
      receptors which only weakly interact with N-CoR and SMRT.
FAU - Mathur, M
AU  - Mathur M
AD  - Division of Clinical and Molecular Endocrinology, Department of Medicine, New 
      York University School of Medicine, New York, New York 10016, USA.
FAU - Tucker, P W
AU  - Tucker PW
FAU - Samuels, H H
AU  - Samuels HH
LA  - eng
GR  - P30 CA016087/CA/NCI NIH HHS/United States
GR  - AR02083/AR/NIAMS NIH HHS/United States
GR  - DK16636/DK/NIDDK NIH HHS/United States
GR  - R01 DK016636/DK/NIDDK NIH HHS/United States
GR  - R56 DK016636/DK/NIDDK NIH HHS/United States
GR  - K01 AR002083/AR/NIAMS NIH HHS/United States
GR  - CA16087/CA/NCI NIH HHS/United States
GR  - AI18016/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (PTB-Associated Splicing Factor)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Repressor Proteins)
RN  - 0 (SIN3A transcription factor)
RN  - EC 3.5.1.98 (Sin3 Histone Deacetylase and Corepressor Complex)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - DNA-Binding Proteins/genetics/metabolism
MH  - HeLa Cells
MH  - Humans
MH  - Mice
MH  - PTB-Associated Splicing Factor
MH  - Plasmids
MH  - Protein Binding
MH  - RNA Splicing
MH  - RNA-Binding Proteins/genetics/*metabolism
MH  - Receptors, Cytoplasmic and Nuclear/genetics/*metabolism
MH  - Repressor Proteins/genetics/*metabolism
MH  - *Signal Transduction/genetics
MH  - Sin3 Histone Deacetylase and Corepressor Complex
PMC - PMC86864
EDAT- 2001/03/22 10:00
MHDA- 2001/04/17 10:01
PMCR- 2001/04/01
CRDT- 2001/03/22 10:00
PHST- 2001/03/22 10:00 [pubmed]
PHST- 2001/04/17 10:01 [medline]
PHST- 2001/03/22 10:00 [entrez]
PHST- 2001/04/01 00:00 [pmc-release]
AID - 1438 [pii]
AID - 10.1128/MCB.21.7.2298-2311.2001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2001 Apr;21(7):2298-311. doi: 10.1128/MCB.21.7.2298-2311.2001.