Casein kinase 2 binds to and phosphorylates BRCA1.
The BRCA1 gene encodes a complex protein that appears to be involved in some aspects of DNA repair, transcription, or cell cycle regulation. The phosphorylation of BRCA1 is enhanced following episodes of DNA damage or during cell cycle progression, indicating that phosphorylation may be an important regulatory mechanism. Through a yeast two hybrid assay, we found that the beta-subunit of casein kinase 2 (CK2) associated with a carboxy-terminal region of BRCA1. This association was much weaker with the same fragment bearing a missense mutation (M1775R) that has been identified in breast tumors. The interaction was also evident in Sf9 cells. Subsequent studies showed that BRCA1 was phosphorylated in vitro by CK2. An analysis by site directed mutagenesis of BRCA1 showed that in vitro phosphorylation by CK2 required a serine at aa1572. These data implicate CK2 as a potential mediator of BRCA1 activity.
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, 46285-0424, USA.
K A
KA
O'Brien
S J
SJ
Lemke
K S
KS
Cocke
R N
RN
Rao
R P
RP
Beckmann
D000469:Alkaline Phosphatase / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D001940:Breast / Q000201:enzymology / Q000378:metabolism; D001943:Breast Neoplasms / Q000201:enzymology / Q000235:genetics; D047390:Casein Kinase II; D003001:Cloning, Molecular; D006801:Humans; D007313:Insecta / Q000166:cytology / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D012694:Serine / Q000235:genetics / Q000378:metabolism
D019313:BRCA1 Protein; D011993:Recombinant Fusion Proteins; D012694:Serine; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases; D000469:Alkaline Phosphatase