PMID- 9121431
OWN - NLM
STAT- MEDLINE
DCOM- 19970424
LR  - 20210526
IS  - 0270-7306 (Print)
IS  - 1098-5549 (Electronic)
IS  - 0270-7306 (Linking)
VI  - 17
IP  - 4
DP  - 1997 Apr
TI  - AF-2 activity and recruitment of steroid receptor coactivator 1 to the estrogen 
      receptor depend on a lysine residue conserved in nuclear receptors.
PG  - 1832-9
AB  - Hormone-dependent transcriptional activation by nuclear receptors depends on the 
      presence of a conserved C-terminal amphipathic alpha-helix (helix 12) in the 
      ligand-binding domain. Here we show that a lysine residue, which is conserved in 
      most nuclear receptors in the predicted helix 3, is also required for 
      estrogen-dependent transactivation. The replacement of lysine 366 with alanine 
      appreciably reduced activation function 2 (AF-2) activity without affecting 
      steroid- or DNA-binding activity in the mouse estrogen receptor. The mutation 
      dramatically reduced the ability of the receptor to bind steroid receptor 
      coactivator 1 (SRC-1) but had no effect on receptor-interacting protein 140 
      (RIP-140) binding, indicating that while their sites of interaction overlap, they 
      are not entirely consistent and in keeping with the proposal that the recruitment 
      of coactivators, such as SRC-1, is required for AF-2 activity. Although the 
      function of RIP-140 remains to be established, RIP-140 appears to be capable of 
      recruiting the basal transcription machinery, since overexpression of the protein 
      markedly increased the transcriptional activity of the mutant receptor. Since the 
      lysine residue is conserved, we propose that it is required, together with 
      residues in helix 12, to form the surface by which members of the nuclear 
      receptor family interact with coactivators.
FAU - Henttu, P M
AU  - Henttu PM
AD  - Molecular Endocrinology Laboratory, Imperial Cancer Research Fund, London, United 
      Kingdom.
FAU - Kalkhoven, E
AU  - Kalkhoven E
FAU - Parker, M G
AU  - Parker MG
LA  - eng
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 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Nuclear Receptor Coactivator 2)
RN  - 0 (Nuclear Receptor Interacting Protein 1)
RN  - 0 (Oligodeoxyribonucleotides)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Receptors, Estrogen)
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 (Ncoa1 protein, mouse)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - K3Z4F929H6 (Lysine)
SB  - IM
MH  - Adaptor Proteins, Signal Transducing
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Conserved Sequence
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Lysine/genetics
MH  - Mice
MH  - Molecular Sequence Data
MH  - Mutagenesis, Site-Directed
MH  - Nuclear Proteins/*metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Nuclear Receptor Coactivator 2
MH  - Nuclear Receptor Interacting Protein 1
MH  - Oligodeoxyribonucleotides/genetics
MH  - Receptors, Cytoplasmic and Nuclear/chemistry/genetics/*metabolism
MH  - Receptors, Estrogen/*metabolism
MH  - Sequence Homology, Amino Acid
MH  - Transcription Factors/*metabolism
MH  - Transcriptional Activation
PMC - PMC232030
EDAT- 1997/04/01 00:00
MHDA- 1997/04/01 00:01
PMCR- 1997/04/01
CRDT- 1997/04/01 00:00
PHST- 1997/04/01 00:00 [pubmed]
PHST- 1997/04/01 00:01 [medline]
PHST- 1997/04/01 00:00 [entrez]
PHST- 1997/04/01 00:00 [pmc-release]
AID - 10.1128/MCB.17.4.1832 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1997 Apr;17(4):1832-9. doi: 10.1128/MCB.17.4.1832.