We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
The negative role of cyclin G in ATM-dependent p53 activation.
- Authors
Ohtsuka, Takao; Jensen, Michael R.; Kim, Hyung Gu; Kim, Kyung-tae; Lee, Sam W.
- Abstract
Cyclin G is one of the earliest p53 target genes to be identified, but its function in the p53 pathway has been elusive. Although the precise mechanisms of cyclin G in this novel network have not been explored, recent studies have demonstrated that cyclin G is a key regulator of the p53-Mdm2 network. Here we present evidence that cyclin G-mediated p53 regulation is dependent upon the status of ataxia-telangiectasia mutated (ATM) protein, which activates p53 in response to DNA damage. Abrogation of cyclin G enhances p53 accumulation and phosphorylation of p53 at the Ser-15 residue, resulting in cell cycle arrest. Ectopically expressed cyclin G significantly reduces the steady-state levels of p53 as well as that of phosphorylated p53 at Ser-15 after DNA damage in normal human dermal fibroblasts containing normal ATM. However, cyclin G does not cause similar reductions in p53 levels in ATM-mutated cells. We also show that translocation of cyclin G to the nucleus requires functional ATM. Thus, our findings identify a new role of cyclin G in ATM-dependent p53 regulation and in cell cycle regulation during DNA damage.Oncogene (2004) 23, 5405-5408. doi:10.1038/sj.onc.1207693 Published online 12 April 2004
- Subjects
CYCLINS; GROWTH factors; CYTOKINES; CELL cycle; BIOLOGICAL rhythms; CELL proliferation; DNA damage
- Publication
Oncogene, 2004, Vol 23, Issue 31, p5405
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1207693