PMID- 10478845
OWN - NLM
STAT- MEDLINE
DCOM- 19991020
LR  - 20171116
IS  - 0888-8809 (Print)
IS  - 0888-8809 (Linking)
VI  - 13
IP  - 9
DP  - 1999 Sep
TI  - Coactivators for the orphan nuclear receptor RORalpha.
PG  - 1550-7
AB  - A mutation in the nuclear orphan receptor RORalpha results in a severe impairment
      of cerebellar development by unknown mechanisms. We have shown previously that
      RORalpha contains a strong constitutive activation domain in its C terminus. We
      therefore searched for mammalian RORalpha coactivators using the minimal
      activation domain as bait in a two-hybrid screen. Several known and putative
      coactivators were isolated, including glucocorticoid receptor-interacting
      protein-1 (GRIP-1) and peroxisome proliferator-activated receptor (PPAR)-binding 
      protein (PBP/TRAP220/DRIP205). These interactions were confirmed in vitro and
      require the intact activation domain of RORalpha although different requirements 
      for interaction with GRIP-1 and PBP were detected. Even in the absence of
      exogenous ligand, RORalpha interacts with a complex or complexes of endogenous
      proteins, similar to those that bind to ligand-occupied thyroid hormone and
      vitamin D receptors. Both PBP and GRIP-1 were shown to be present in these
      complexes. Thus we have identified several potential RORalpha coactivators that, 
      in contrast to the interactions with hormone receptors, interact with RORalpha in
      yeast, in bacterial extracts, and in mammalian cells in vivo and in vitro in the 
      absence of exogenous ligand. GRIP-1 functioned as a coactivator for the RORalpha 
      both in yeast and in mammalian cells. Thus, GRIP-1 is the first proven
      coactivator for RORalpha.
FAU - Atkins, G B
AU  - Atkins GB
AD  - Department of Medicine, The Penn Diabetes Center, University of Pennsylvania
      School of Medicine, Philadelphia 19104-6149, USA.
FAU - Hu, X
AU  - Hu X
FAU - Guenther, M G
AU  - Guenther MG
FAU - Rachez, C
AU  - Rachez C
FAU - Freedman, L P
AU  - Freedman LP
FAU - Lazar, M A
AU  - Lazar MA
LA  - eng
GR  - DK-45586/DK/NIDDK NIH HHS/United States
GR  - GM-08216-12/GM/NIGMS NIH HHS/United States
GR  - P30 DK-50306/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Mol Endocrinol
JT  - Molecular endocrinology (Baltimore, Md.)
JID - 8801431
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Carrier Proteins)
RN  - 0 (Cell Extracts)
RN  - 0 (LIM Domain Proteins)
RN  - 0 (MED1 protein, human)
RN  - 0 (Med1 protein, mouse)
RN  - 0 (Mediator Complex Subunit 1)
RN  - 0 (NCOA2 protein, human)
RN  - 0 (Ncoa2 protein, mouse)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 1)
RN  - 0 (PSMC5 protein, human)
RN  - 0 (RORA protein, human)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
RN  - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
SB  - IM
MH  - ATPases Associated with Diverse Cellular Activities
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Binding Sites/genetics
MH  - Carrier Proteins/genetics/metabolism
MH  - Cell Extracts
MH  - Cell Line
MH  - Cell-Free System/metabolism
MH  - *Gene Expression Regulation
MH  - Humans
MH  - LIM Domain Proteins
MH  - Mediator Complex Subunit 1
MH  - Mice
MH  - Mutation
MH  - Nuclear Receptor Coactivator 2
MH  - Nuclear Receptor Subfamily 1, Group F, Member 1
MH  - Proteasome Endopeptidase Complex
MH  - Protein Binding
MH  - Receptors, Cytoplasmic and Nuclear/chemistry/*genetics/metabolism
MH  - Saccharomyces cerevisiae/genetics
MH  - Trans-Activators/chemistry/*genetics/metabolism
MH  - Transcription Factors/genetics/metabolism
EDAT- 1999/09/09 00:00
MHDA- 1999/09/09 00:01
CRDT- 1999/09/09 00:00
PHST- 1999/09/09 00:00 [pubmed]
PHST- 1999/09/09 00:01 [medline]
PHST- 1999/09/09 00:00 [entrez]
AID - 10.1210/mend.13.9.0343 [doi]
PST - ppublish
SO  - Mol Endocrinol. 1999 Sep;13(9):1550-7. doi: 10.1210/mend.13.9.0343.