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

Takao Ohtsuka1, Michael R Jensen, Hyung Gu Kim

  • 1Cancer Biology Program, Hematology/Oncology Division, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.

Oncogene
|April 13, 2004
PubMed

Insights

Cyclin G regulates the p53 pathway by depending on ATM protein status. Loss of cyclin G increases p53 levels and cell cycle arrest, while its presence reduces p53 after DNA damage in an ATM-dependent manner.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Genetics

Background:

  • Cyclin G is an early p53 target gene with an unclear role in the p53 pathway.
  • Recent research suggests cyclin G is a key regulator of the p53-Mdm2 network.

Purpose of the Study:

  • To investigate the role of cyclin G in p53 regulation.
  • To determine the dependence of cyclin G's function on ataxia-telangiectasia mutated (ATM) protein status.

Main Methods:

  • Studied p53 accumulation and phosphorylation at Ser-15 in response to DNA damage.
  • Examined the effect of cyclin G abrogation and ectopic expression.
  • Assessed cyclin G nuclear translocation in ATM-proficient and ATM-mutated cells.

Main Results:

  • Abrogation of cyclin G enhanced p53 accumulation and phosphorylation, leading to cell cycle arrest.
  • Ectopic cyclin G reduced p53 levels post-DNA damage in ATM-normal cells but not in ATM-mutated cells.
  • Functional ATM was required for cyclin G's nuclear translocation.

Conclusions:

  • Cyclin G plays a novel role in ATM-dependent p53 regulation.
  • Cyclin G influences cell cycle regulation during DNA damage response through an ATM-dependent mechanism.

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