Posttranslational Modifications Regulate HIPK2, a Driver of Proliferative Diseases

J Mol Med (Berl). 2013 Sep;91(9):1051-8. doi: 10.1007/s00109-013-1042-0. Epub 2013 Apr 25.

Abstract

The serine/threonine kinase homeodomain-interacting protein kinase (HIPK2) is a tumor suppressor and functions as an evolutionary conserved regulator of signaling and gene expression. This kinase regulates a surprisingly vast array of biological processes that range from the DNA damage response and apoptosis to hypoxia signaling and cell proliferation. Recent studies show the tight control of HIPK2 by hierarchically occurring posttranslational modifications such as phosphorylation, small ubiquitin-like modifier modification, acetylation, and ubiquitination. The physiological function of HIPK2 as a regulator of cell proliferation and survival has a downside: proliferative diseases. Dysregulation of HIPK2 can result in increased proliferation of cell populations as it occurs in cancer or fibrosis. We discuss various models that could explain how inappropriate expression, modification, or localization of HIPK2 can be a driver for these proliferative diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Carrier Proteins / physiology*
  • Cell Differentiation
  • Fibrosis / metabolism
  • Humans
  • Neoplasms / metabolism
  • Protein Processing, Post-Translational*
  • Protein-Serine-Threonine Kinases / physiology*

Substances

  • Carrier Proteins
  • HIPK2 protein, human
  • Hipk2 protein, mouse
  • Protein-Serine-Threonine Kinases