PMID- 9774463
OWN - NLM
STAT- MEDLINE
DCOM- 19981112
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 273
IP  - 43
DP  - 1998 Oct 23
TI  - Different classes of coactivators recognize distinct but overlapping binding 
      sites on the estrogen receptor ligand binding domain.
PG  - 28371-7
AB  - We have analyzed interaction of coactivators with the wild-type estrogen receptor 
      alpha (ER), HEG0, and a mutant, L536P-HEG0, which is constitutively active in 
      several transiently transfected cells and a HeLa line that stably propagates an 
      estrogen-sensitive reporter gene. Different classes of coactivators do not 
      recognize the ER ligand binding domain (LBD) in the same manner. Steroid receptor 
      coactivator-1 (SRC-1), amplified in breast cancer-1 (AIB-1), transcriptional 
      intermediary factor-1 (TIF-1), transcriptional intermediary factor-2 (TIF-2), and 
      receptor interacting protein 140 (RIP140) interacted with HEG0 and L536P-HEG0 in 
      the presence of estradiol, but generally not in the presence of anti-estrogens. 
      However, ICI164,384 stimulated some interaction of RIP140 with LBDs. SRC-1, 
      AIB-1, and RIP140 interacted constitutively with the L536P ER, whereas TIF-1 and 
      TIF-2 interacted only weakly in the absence of hormone. Reciprocal competition 
      for binding to the ER LBD was observed between different classes of coactivators. 
      Moreover, coexpression of RIP140 blocked enhanced transactivation by HEG0 
      observed in the presence of TIF-2, suggesting that RIP140 may play a negative 
      role in ER signaling. We conclude that constitutive activity of L536P-HEG0 is 
      manifested to similar degrees in different cell types and likely arises from 
      constitutive coactivator binding; different classes of coactivators recognize 
      distinct but overlapping binding sites on the ER LBD. Finally, the observation 
      that L536P-HEG0 interacted constitutively with AIB-1, a coactivator that has been 
      implicated in ER signaling in breast and ovarian cancer, suggests that similar 
      mutations in the ER may contribute to hormone-independent proliferation of breast 
      and ovarian cells.
FAU - Eng, F C
AU  - Eng FC
AD  - Departments of Physiology and Medicine, McGill University, Montreal H3G 1Y6, 
      Canada.
FAU - Barsalou, A
AU  - Barsalou A
FAU - Akutsu, N
AU  - Akutsu N
FAU - Mercier, I
AU  - Mercier I
FAU - Zechel, C
AU  - Zechel C
FAU - Mader, S
AU  - Mader S
FAU - White, J H
AU  - White JH
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 (Estrogens)
RN  - 0 (Ligands)
RN  - 0 (NRIP1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nuclear Receptor Interacting Protein 1)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Transcription Factors)
RN  - 0 (transcriptional intermediary factor 1)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - Binding Sites
MH  - Binding, Competitive
MH  - Breast Neoplasms/metabolism
MH  - COS Cells
MH  - Estrogens/metabolism
MH  - Female
MH  - HeLa Cells
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Ligands
MH  - Mutation
MH  - Nuclear Proteins/metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Nuclear Receptor Interacting Protein 1
MH  - Ovarian Neoplasms/metabolism
MH  - Peptide Fragments/genetics/metabolism
MH  - Protein Binding
MH  - Receptors, Estrogen/genetics/*metabolism
MH  - Recombinant Fusion Proteins/metabolism
MH  - Signal Transduction
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
EDAT- 1998/10/17 00:00
MHDA- 1998/10/17 00:01
CRDT- 1998/10/17 00:00
PHST- 1998/10/17 00:00 [pubmed]
PHST- 1998/10/17 00:01 [medline]
PHST- 1998/10/17 00:00 [entrez]
AID - S0021-9258(19)59606-5 [pii]
AID - 10.1074/jbc.273.43.28371 [doi]
PST - ppublish
SO  - J Biol Chem. 1998 Oct 23;273(43):28371-7. doi: 10.1074/jbc.273.43.28371.