PMID- 10428798
OWN - NLM
STAT- MEDLINE
DCOM- 19990902
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 32
DP  - 1999 Aug 6
TI  - Potentiation of human estrogen receptor alpha transcriptional activation through 
      phosphorylation of serines 104 and 106 by the cyclin A-CDK2 complex.
PG  - 22296-302
AB  - Both estradiol binding and phosphorylation regulate transcriptional activation by
      the human estrogen receptor alpha (ER). We have previously shown that activation 
      of the cyclin A-CDK2 complex by overexpression of cyclin A leads to enhanced
      ER-dependent transcriptional activation and that the cyclin A-CDK2 complex
      phosphorylates the ER N-terminal activation function-1 (AF-1) between residues 82
      and 121. Within ER AF-1, serines 104, 106, and 118 represent potential CDK
      phosphorylation sites, and in this current study, we ascertain their importance
      in mediating cyclin A-CDK2-dependent enhancement of ER transcriptional activity. 
      Cyclin A overexpression does not enhance transcriptional activation by an ER
      derivative bearing serine-to-alanine changes at residues 104, 106, and 118.
      Likewise, the cyclin A-CDK2 complex does not phosphorylate this triple-mutated
      derivative in vitro. Individual serine-to-alanine mutations at residues 104 and
      106, but not 118, decrease ER-dependent transcriptional enhancement in response
      to cyclin A. The same relationship holds for ER phosphorylation by cyclin A-CDK2 
      in vitro. Finally, enhancement of ER transcriptional activation by cyclin A is
      evident in the absence and presence of estradiol, as well as in the presence of
      tamoxifen, suggesting that the effect of the cyclin A-CDK2 on ER transcriptional 
      activation is AF-2-independent. These results indicate that the enhancement of ER
      transcriptional activation by the cyclin A-CDK2 complex is mediated via the AF-1 
      domain by phosphorylation of serines 104 and 106. We propose that these residues 
      control ER AF-1 activity in response to signals that affect cyclin A-CDK2
      function.
FAU - Rogatsky, I
AU  - Rogatsky I
AD  - Department of Microbiology and the Kaplan Comprehensive Cancer Center, New York
      University School of Medicine, New York, New York 10016, USA.
FAU - Trowbridge, J M
AU  - Trowbridge JM
FAU - Garabedian, M J
AU  - Garabedian MJ
LA  - eng
GR  - 5T32AI07180-17/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Cyclin A)
RN  - 0 (Estrogen Receptor alpha)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Recombinant Proteins)
RN  - 452VLY9402 (Serine)
RN  - 4TI98Z838E (Estradiol)
RN  - EC 2.7.11.1 (Protein-Serine-Threonine Kinases)
RN  - EC 2.7.11.22 (CDC2-CDC28 Kinases)
RN  - EC 2.7.11.22 (CDK2 protein, human)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinase 2)
RN  - EC 2.7.11.22 (Cyclin-Dependent Kinases)
SB  - IM
MH  - *CDC2-CDC28 Kinases
MH  - Cyclin A/genetics/*metabolism
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Estradiol/metabolism
MH  - Estrogen Receptor alpha
MH  - Humans
MH  - Models, Genetic
MH  - Mutagenesis, Site-Directed
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Receptors, Estrogen/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Serine/genetics/*metabolism
MH  - *Transcriptional Activation
EDAT- 1999/07/31 00:00
MHDA- 1999/07/31 00:01
CRDT- 1999/07/31 00:00
PHST- 1999/07/31 00:00 [pubmed]
PHST- 1999/07/31 00:01 [medline]
PHST- 1999/07/31 00:00 [entrez]
AID - 10.1074/jbc.274.32.22296 [doi]
AID - S0021-9258(18)81541-1 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Aug 6;274(32):22296-302. doi: 10.1074/jbc.274.32.22296.