The human DNA-activated protein kinase, DNA-PK: Substrate specificity
- Brookhaven National Lab., Upton, NY (United States). Biology Dept.
- Univ. of Calgary, Alberta (Canada). Dept. of Biological Sciences
- National Institutes of Health, Bethesda, MD (United States). Lab. of Cell Biology
Although much has been learned about the structure and function of p53 and the probable sequence of subsequent events that lead to cell cycle arrest, little is known about how DNA damage is detected and the nature of the signal that is generated by DNA damage. Circumstantial evidence suggests that protein kinases may be involved. In vitro, human DNA-PK phosphorylates a variety of nuclear DNA-binding, regulatory proteins including the tumor suppressor protein p53, the single-stranded DNA binding protein RPA, the heat shock protein hsp90, the large tumor antigen (TAg) of simian virus 40, a variety of transcription factors including Fos, Jun, serum response factor (SRF), Myc, Sp1, Oct-1, TFIID, E2F, the estrogen receptor, and the large subunit of RNA polymerase II (reviewed in Anderson, 1993; Jackson et al., 1993). However, for most of these proteins, the sites that are phosphorylated by DNA-PK are not known. To determine if the sites that were phosphorylated in vitro also were phosphorylated in vivo and if DNA-PK recognized a preferred protein sequence, the authors identified the sites phosphorylated by DNA-PK in several substrates by direct protein sequence analysis. Each phosphorylated serine or threonine is followed immediately by glutamine in the polypeptide chain; at no other positions are the amino acid residues obviously constrained.
- Research Organization:
- Brookhaven National Lab. (BNL), Upton, NY (United States)
- Sponsoring Organization:
- USDOE, Washington, DC (United States); Natural Sciences and Engineering Research Council of Canada, Ottawa, ON (Canada); Alberta Cancer Board, AB (Canada)
- DOE Contract Number:
- AC02-76CH00016
- OSTI ID:
- 113929
- Report Number(s):
- BNL-62179; ON: DE96000414; TRN: AHC29526%%73
- Resource Relation:
- Other Information: PBD: 5 Nov 1994
- Country of Publication:
- United States
- Language:
- English
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