Enhanced phosphorylation of p53 serine 18 following DNA damage in DNA-dependent protein kinase catalytic subunit-deficient cells

Citation
R. Araki et al., Enhanced phosphorylation of p53 serine 18 following DNA damage in DNA-dependent protein kinase catalytic subunit-deficient cells, CANCER RES, 59(15), 1999, pp. 3543-3546
Citations number
21
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
00085472 → ACNP
Volume
59
Issue
15
Year of publication
1999
Pages
3543 - 3546
Database
ISI
SICI code
0008-5472(19990801)59:15<3543:EPOPS1>2.0.ZU;2-P
Abstract
DNA-dependent protein kinase (DNA-PK) controls signal transduction followin g DNA damage. However, the molecular mechanism of the signal transduction h as been elusive. A number of candidates for substrates of DNA-PK have been reported on the basis of the in vitro assay system. In particular, the Ser- 15 amino acid residue in p53 was one of the first such in vitro substrates to be described, and it has drawn considerable attention due to its biologi cal significance. Moreover, p53 Ser-15 is a site that has been shown to be phosphorylated in response to DNA damage. In addition, crucial evidence ind icating that DNA-PK controls the transactivation of p53 following DNA damag e was reported quite recently. To clarify these important issues, we conducted the experiments with dna-pk cs null mutant cells, including gene knockout cells. As a result, we detect ed enhanced phosphorylation of p53 Ser-18, which corresponds to Ser-15 of h uman p53, and significant expression of p21 and mdm2 following ionizing rad iation. Furthermore, we identified a missense point mutation in the p53 DNA -binding motif region in SCGR11 cells, which were established from severe c ombined immunodeficient (SCID) mice and used for previous study on the role of DNA-PK in p53 transactivation. Our observation clearly indicates that DNA-PK catalytic subunit does not ph osphorylate p53 Ser-18 in vivo or control the transactivation of p53 in res ponse to DNA damage, and these results further emphasize the different path ways in which ataxia telangiectasia-mutated (ATM);and DNA-PK operate follow ing radiation damage.