PMID- 10373534
OWN - NLM
STAT- MEDLINE
DCOM- 19990722
LR  - 20190508
IS  - 0270-7306 (Print)
IS  - 0270-7306 (Linking)
VI  - 19
IP  - 7
DP  - 1999 Jul
TI  - BRCA1 is phosphorylated at serine 1497 in vivo at a cyclin-dependent kinase 2
      phosphorylation site.
PG  - 4843-54
AB  - BRCA1 is a cell cycle-regulated nuclear protein that is phosphorylated mainly on 
      serine and to a lesser extent on threonine residues. Changes in phosphorylation
      occur in response to cell cycle progression and DNA damage. Specifically, BRCA1
      undergoes hyperphosphorylation during late G1 and S phases of the cell cycle.
      Here we report that BRCA1 is phosphorylated in vivo at serine 1497 (S1497), which
      is part of a cyclin-dependent kinase (CDK) consensus site. S1497 can be
      phosphorylated in vitro by CDK2-cyclin A or E. BRCA1 coimmunoprecipitates with an
      endogenous serine-threonine protein kinase activity that phosphorylates S1497 in 
      vitro. This cellular kinase activity is sensitive to transfection of a dominant
      negative form of CDK2 as well as the application of the CDK inhibitors p21 and
      butyrolactone I but not p16. Furthermore, BRCA1 coimmunoprecipitates with CDK2
      and cyclin A. These results suggest that the endogenous kinase activity is
      composed of CDK2-cyclin complexes, at least in part, concordant with the
      G1/S-specific increase in BRCA1 phosphorylation.
FAU - Ruffner, H
AU  - Ruffner H
AD  - The Salk Institute, La Jolla, California 92037, USA.
FAU - Jiang, W
AU  - Jiang W
FAU - Craig, A G
AU  - Craig AG
FAU - Hunter, T
AU  - Hunter T
FAU - Verma, I M
AU  - Verma IM
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 (BRCA1 Protein)
RN  - 0 (Cyclin A)
RN  - 0 (Cyclin E)
RN  - 2ZD004190S (Threonine)
RN  - 452VLY9402 (Serine)
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  - BRCA1 Protein/genetics/*metabolism
MH  - Binding Sites
MH  - *CDC2-CDC28 Kinases
MH  - Cell Line, Transformed
MH  - Cyclin A/metabolism
MH  - Cyclin E/metabolism
MH  - Cyclin-Dependent Kinase 2
MH  - Cyclin-Dependent Kinases/*metabolism
MH  - Humans
MH  - Phosphorylation
MH  - Protein-Serine-Threonine Kinases/*metabolism
MH  - Serine/*metabolism
MH  - Substrate Specificity
MH  - Threonine/metabolism
PMC - PMC84283
EDAT- 1999/06/22 00:00
MHDA- 1999/06/22 00:01
CRDT- 1999/06/22 00:00
PHST- 1999/06/22 00:00 [pubmed]
PHST- 1999/06/22 00:01 [medline]
PHST- 1999/06/22 00:00 [entrez]
AID - 10.1128/mcb.19.7.4843 [doi]
PST - ppublish
SO  - Mol Cell Biol. 1999 Jul;19(7):4843-54. doi: 10.1128/mcb.19.7.4843.