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Homeodomain interacting protein kinase 2 promotes apoptosis by downregulating the transcriptional corepressor CtBP

Qinghong Zhang1, Yasuhiro Yoshimatsu, Jeffrey Hildebrand

  • 1Vollum Institute, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA. zhangq@ohsu.edu

Cell
|October 22, 2003
PubMed

Insights

Genetic knockout of CtBP (C-terminal binding protein) increases apoptosis. UV radiation and HIPK2 (homeodomain interacting protein kinase 2) reduce CtBP levels, promoting apoptosis in p53-deficient cells.

Area of Science:

  • Molecular Biology
  • Cell Biology
  • Cancer Research

Background:

  • Transcriptional corepressor CtBP (C-terminal binding protein) plays a role in regulating gene expression.
  • CtBP knockout in mouse embryo fibroblasts leads to increased apoptosis.
  • Understanding CtBP regulation is crucial for deciphering apoptosis pathways.

Purpose of the Study:

  • To identify pathways regulating cellular CtBP levels and its role in apoptosis.
  • To investigate the link between CtBP, HIPK2 (homeodomain interacting protein kinase 2), and UV-induced apoptosis.

Main Methods:

  • Screening of a mouse embryo cDNA library using an E1A-CtBP complex.
  • Utilizing genetic knockout, siRNA, and kinase-inactive mutants to study protein function.
  • Assessing apoptosis induction in p53-deficient cells.

Main Results:

  • HIPK2 was identified as a protein interacting with CtBP.
  • HIPK2 expression or UV irradiation reduced CtBP levels through proteasome-mediated degradation.
  • UV-induced CtBP reduction was dependent on HIPK2 kinase activity.
  • Reduced CtBP levels promoted apoptosis, even in p53-deficient cells.

Conclusions:

  • A novel pathway for UV-induced apoptosis involving HIPK2-mediated CtBP degradation has been elucidated.
  • This pathway is functional in cells lacking p53, offering insights into alternative apoptotic mechanisms.
  • Findings highlight CtBP regulation as a key factor in cellular apoptosis.

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