PMID- 11113179
OWN - NLM
STAT- MEDLINE
DCOM- 20010118
LR  - 20231105
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 21
IP  - 1
DP  - 2001 Jan
TI  - Analysis of the steroid receptor coactivator 1 (SRC1)-CREB binding protein 
      interaction interface and its importance for the function of SRC1.
PG  - 39-50
AB  - The transcriptional activity of nuclear receptors is mediated by coactivator 
      proteins, including steroid receptor coactivator 1 (SRC1) and its homologues and 
      the general coactivators CREB binding protein (CBP) and p300. SRC1 contains an 
      activation domain (AD1) which functions via recruitment of CBP and and p300. In 
      this study, we have used yeast two-hybrid and in vitro interaction-peptide 
      inhibition experiments to map the AD1 domain of SRC1 to a 35-residue sequence 
      potentially containing two alpha-helices. We also define a 72-amino-acid sequence 
      in CBP necessary for SRC1 binding, designated the SRC1 interaction domain (SID). 
      We show that in contrast to SRC1, direct binding of CBP to the estrogen receptor 
      is weak, suggesting that SRC1 functions primarily as an adaptor to recruit CBP 
      and p300. In support of this, we show that the ability of SRC1 to enhance 
      ligand-dependent nuclear receptor activity in transiently transfected cells is 
      dependent upon the integrity of the AD1 region. In contrast, the putative histone 
      acetyltransferase domain, the Per-Arnt-Sim basic helix-loop-helix domain, the 
      glutamine-rich domain, and AD2 can each be removed without loss of ligand-induced 
      activity. Remarkably, a construct corresponding to residues 631 to 970, which 
      contains only the LXXLL motifs and the AD1 region of SRC1, retained strong 
      coactivator activity in our assays.
FAU - Sheppard, H M
AU  - Sheppard HM
AD  - Department of Biochemistry, University of Leicester, Leicester, LE1 7RH, United 
      Kingdom.
FAU - Harries, J C
AU  - Harries JC
FAU - Hussain, S
AU  - Hussain S
FAU - Bevan, C
AU  - Bevan C
FAU - Heery, D M
AU  - Heery DM
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Cell Biol
JT  - Molecular and cellular biology
JID - 8109087
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - EC 2.3.1.48 (CREB-Binding Protein)
RN  - EC 2.3.1.48 (CREBBP protein, human)
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  - Amino Acid Motifs
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - CREB-Binding Protein
MH  - Cell Line
MH  - Genes, Reporter
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Molecular Sequence Data
MH  - Mutation
MH  - Nuclear Proteins/chemistry/genetics/*metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Peptide Fragments/chemistry/genetics/metabolism
MH  - Protein Binding
MH  - Protein Structure, Secondary
MH  - Protein Structure, Tertiary
MH  - Receptors, Estrogen/metabolism
MH  - Response Elements/genetics
MH  - Saccharomyces cerevisiae/genetics
MH  - Thermodynamics
MH  - Trans-Activators/chemistry/genetics/*metabolism
MH  - Transcription Factors/chemistry/genetics/*metabolism
MH  - Transfection
MH  - Two-Hybrid System Techniques
PMC - PMC86566
EDAT- 2000/12/13 11:00
MHDA- 2001/02/28 10:01
PMCR- 2001/01/01
CRDT- 2000/12/13 11:00
PHST- 2000/12/13 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/12/13 11:00 [entrez]
PHST- 2001/01/01 00:00 [pmc-release]
AID - 0940 [pii]
AID - 10.1128/MCB.21.1.39-50.2001 [doi]
PST - ppublish
SO  - Mol Cell Biol. 2001 Jan;21(1):39-50. doi: 10.1128/MCB.21.1.39-50.2001.