PMID- 10364267
OWN - NLM
STAT- MEDLINE
DCOM- 19990715
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 25
DP  - 1999 Jun 18
TI  - Receptor interacting protein RIP140 inhibits both positive and negative gene
      regulation by glucocorticoids.
PG  - 18121-7
AB  - Recent development in the field of gene regulation by nuclear receptors (NRs)
      have identified a role for cofactors in transcriptional control. While some of
      the NR-associated proteins serve as coactivators, the effect of the receptor
      interacting protein 140 (RIP140) on NR transcriptional responses is complex. In
      this report we have studied the effect of RIP140 on gene regulation by the
      glucocorticoid receptor (GR). We demonstrate that RIP140 antagonized all
      GR-mediated responses tested, which included activation through classical GRE,
      the synergistic effects of glucocorticoids on AP-1 and Pbx1/HOXB1 responsive
      elements, as well as gene repression through a negative GRE and cross-talk with
      NF-kappaB (RelA). This involved the ligand-binding domain of the GR and did not
      occur when the GR was bound to the antagonist RU486. The strong repressive effect
      of RIP140 was restricted to glucocorticoid-mediated responses in as much as it
      slightly increased signaling through the RelA and the Pit-1/Pbx proteins and only
      slightly repressed signaling through the Pbx1/HOXB1 and AP-1 proteins, excluding 
      general squelching as a mechanism. Instead, this suggests that RIP140 acts as a
      direct inhibitor of GR function. In line with a direct effect of RIP140 on the
      GR, we demonstrate a GR-RIP140 interaction in vitro by a glutathione
      S-transferase-pull down assay. Furthermore, the repressive effect of RIP140 could
      partially be overcome by overexpression of the coactivator TIF2, which involved a
      competition between TIF2 and RIP140 for binding to the GR.
FAU - Subramaniam, N
AU  - Subramaniam N
AD  - Department, Karolinska Institutet, Huddinge University Hospital, F60 Novum,
      SE-141 86 Huddinge, Sweden.
FAU - Treuter, E
AU  - Treuter E
FAU - Okret, S
AU  - Okret S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Glucocorticoids)
RN  - 0 (NCOA2 protein, human)
RN  - 0 (NRIP1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Nuclear Receptor Interacting Protein 1)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Glucocorticoid)
RN  - 0 (Repressor Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Cell Line
MH  - Gene Expression Regulation/*drug effects
MH  - Genes, Reporter
MH  - Glucocorticoids/*pharmacology
MH  - Humans
MH  - Nuclear Proteins/metabolism/*pharmacology
MH  - Nuclear Receptor Coactivator 2
MH  - Nuclear Receptor Interacting Protein 1
MH  - Protein Binding
MH  - Receptors, Cytoplasmic and Nuclear/metabolism
MH  - Receptors, Glucocorticoid/genetics/*metabolism
MH  - Regulatory Sequences, Nucleic Acid
MH  - Repressor Proteins/genetics
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription Factors/genetics
MH  - Transfection
EDAT- 1999/06/11 00:00
MHDA- 1999/06/11 00:01
CRDT- 1999/06/11 00:00
PHST- 1999/06/11 00:00 [pubmed]
PHST- 1999/06/11 00:01 [medline]
PHST- 1999/06/11 00:00 [entrez]
AID - 10.1074/jbc.274.25.18121 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Jun 18;274(25):18121-7. doi: 10.1074/jbc.274.25.18121.