The negative role of cyclin G in ATM-dependent p53 activation

Ohtsuka Takao, Michael R. Jensen, Gu Kim Hyung, Kyung Tae Kim, Sam W. Lee

Research output: Contribution to journalArticle

39 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)5405-5408
Number of pages4
JournalOncogene
Volume23
Issue number31
DOIs
Publication statusPublished - Jul 8 2004
Externally publishedYes

Fingerprint

Cyclin G
Ataxia Telangiectasia
DNA Damage
Ataxia Telangiectasia Mutated Proteins
p53 Genes
Cell Cycle Checkpoints
Cell Cycle
Fibroblasts

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Takao, O., Jensen, M. R., Hyung, G. K., Kim, K. T., & Lee, S. W. (2004). The negative role of cyclin G in ATM-dependent p53 activation. Oncogene, 23(31), 5405-5408. https://doi.org/10.1038/sj.onc.1207693

The negative role of cyclin G in ATM-dependent p53 activation. / Takao, Ohtsuka; Jensen, Michael R.; Hyung, Gu Kim; Kim, Kyung Tae; Lee, Sam W.

In: Oncogene, Vol. 23, No. 31, 08.07.2004, p. 5405-5408.

Research output: Contribution to journalArticle

Takao, O, Jensen, MR, Hyung, GK, Kim, KT & Lee, SW 2004, 'The negative role of cyclin G in ATM-dependent p53 activation', Oncogene, vol. 23, no. 31, pp. 5405-5408. https://doi.org/10.1038/sj.onc.1207693
Takao, Ohtsuka ; Jensen, Michael R. ; Hyung, Gu Kim ; Kim, Kyung Tae ; Lee, Sam W. / The negative role of cyclin G in ATM-dependent p53 activation. In: Oncogene. 2004 ; Vol. 23, No. 31. pp. 5405-5408.
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