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Lats2 phosphorylates p21/CDKN1A after UV irradiation and regulates apoptosis

Hirokazu Suzuki1, Norikazu Yabuta, Nobuhiro Okada

  • 1Department of Molecular Genetics, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita City, Osaka 565-0871, Japan.

Journal of Cell Science
|July 27, 2013
PubMed

Insights

Large tumor suppressor 2 (LATS2) is activated by UV radiation, leading to p21 degradation and apoptosis. This discovery reveals a new LATS2-dependent pathway for cell death induction following DNA damage.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Biochemistry

Background:

  • Large tumor suppressor 2 (LATS2) is a human tumor suppressor gene and a member of the AGC Ser/Thr (S/T) kinase family.
  • p21 (CDKN1A) is a crucial regulator of the cell cycle and apoptosis, inhibiting cyclin-dependent kinases (CDKs) and binding to procaspase-3.

Purpose of the Study:

  • To elucidate the role of LATS2 in cellular response to DNA damage.
  • To investigate the mechanism by which LATS2 influences apoptosis following ultraviolet (UV) radiation exposure.

Main Methods:

  • Investigated LATS2 phosphorylation in response to UV radiation.
  • Assessed the effect of LATS2 phosphorylation on its kinase activity.
  • Examined the downstream targets of LATS2, specifically p21.
  • Analyzed the impact of LATS2 activity on apoptosis and caspase activation.

Main Results:

  • UV radiation induces LATS2 phosphorylation at Ser835 (S835) by Chk1, enhancing LATS2 kinase activity.
  • Activated LATS2 phosphorylates p21 at S146, promoting p21 degradation.
  • LATS2 overexpression leads to p21 degradation, activation of caspase-3 and caspase-9, and ultimately apoptosis.

Conclusions:

  • A novel LATS2-dependent pathway for inducing cell death in response to severe DNA damage has been identified.
  • LATS2 plays a critical role in the apoptotic response to UV-induced DNA damage through p21 regulation.
Keywords:
ApoptosisCDKN1ALats2PhosphorylationUVp21

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