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Regulation of ATM/p53-dependent suppression of myc-induced lymphomas by Wip1 phosphatase

Sathyavageeswaran Shreeram1, Weng Kee Hee, Oleg N Demidov

  • 1Institute of Molecular and Cell Biology, Singapore, 138673.

The Journal of Experimental Medicine
|December 13, 2006
PubMed

Insights

The ataxia telangiectasia mutated (ATM) kinase suppresses tumors by regulating apoptosis. Deleting Wip1 phosphatase up-regulates ATM, delaying B cell lymphoma formation in mice.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • The ataxia telangiectasia mutated (ATM) kinase is a crucial tumor suppressor involved in cell cycle checkpoints and apoptosis.
  • ATM plays a significant role in regulating apoptosis and lymphomagenesis, particularly in the context of c-myc.
  • Wip1 phosphatase inhibits ATM activity.

Purpose of the Study:

  • To investigate the role of ATM in c-myc-induced lymphomagenesis.
  • To determine the effect of Wip1 phosphatase deletion on ATM activity and lymphoma development.
  • To elucidate the regulatory network involving Wip1, ATM, and tumor suppression.

Main Methods:

  • Utilizing mouse genetic crosses to study lymphoma development.
  • Analyzing the impact of Wip1 gene deletion on ATM and p53 pathways.
  • Investigating the dependency on ATM, p53, p38 MAPK, and Arf in myc-induced lymphomas.

Main Results:

  • Deletion of Wip1 phosphatase leads to ATM up-regulation.
  • Wip1 deficiency suppresses Emicro-myc-induced B cell lymphomas.
  • Lymphoma onset is significantly delayed in Wip1-null mice, dependent on ATM and p53, but not p38 MAPK or Arf.

Conclusions:

  • Wip1 phosphatase is a critical regulator of the ATM-mediated tumor surveillance network.
  • Targeting Wip1 could be a therapeutic strategy for ATM-dependent cancers.
  • The interplay between Wip1, ATM, and p53 is vital for preventing lymphomagenesis.

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