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Yeast As a Chassis for Developing Functional Assays to Study Human P53
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Yeast As a Chassis for Developing Functional Assays to Study Human P53

Published on: August 4, 2019

Regulation of p53 activity by HIPK2: molecular mechanisms and therapeutical implications in human cancer cells

R Puca1, L Nardinocchi, D Givol

  • 1Department of Experimental Oncology, Molecular Oncogenesis Laboratory, National Cancer Institute Regina Elena, Rome, Italy.

Oncogene
|June 2, 2010
PubMed

Insights

The tumor suppressor HIPK2 (homeodomain-interacting protein kinase-2) activates p53

Area of Science:

  • Oncology
  • Molecular Biology
  • Cellular Stress Response

Background:

  • The p53 protein is a critical tumor suppressor involved in cellular stress responses.
  • p53 activation after DNA damage initiates gene expression for cell-cycle arrest, DNA repair, senescence, and apoptosis.
  • Post-translational modifications regulate p53 activity and target gene selection.

Purpose of the Study:

  • To elucidate the role of homeodomain-interacting protein kinase-2 (HIPK2) in regulating p53 function.
  • To understand how HIPK2 influences p53-mediated apoptosis and gene expression.
  • To explore the therapeutic potential of targeting the p53-HIPK2 interaction in cancer.

Main Methods:

  • Investigating the phosphorylation of p53 at Ser46 by HIPK2.
  • Analyzing the facilitation of Lys382 acetylation at the p53 C-terminus by HIPK2.
  • Examining the impact of HIPK2 activation by genotoxic agents and its deregulation in tumors (e.g., hypoxia).

Main Results:

  • HIPK2 is a key regulator of p53's apoptotic function.
  • HIPK2 phosphorylates p53 at Ser46 and facilitates C-terminal acetylation.
  • HIPK2 activity can be altered in tumors, affecting p53 pathways.
  • Both active and inactive forms of HIPK2 can unexpectedly influence p53.

Conclusions:

  • HIPK2 is essential for activating p53's pro-apoptotic functions.
  • Dysregulation of HIPK2 in cancer impacts p53 pathway integrity.
  • Targeting p53 and HIPK2 presents promising avenues for cancer diagnostics and therapeutics.

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