Homeodomain-interacting protein kinase-2 phosphorylates p53 at Ser 46 and mediates apoptosis

Nat Cell Biol. 2002 Jan;4(1):11-9. doi: 10.1038/ncb714.

Abstract

Phosphorylation of p53 at Ser 46 was shown to regulate p53 apoptotic activity. Here we demonstrate that homeodomain-interacting protein kinase-2 (HIPK2), a member of a novel family of nuclear serine/threonine kinases, binds to and activates p53 by directly phosphorylating it at Ser 46. HIPK2 localizes with p53 and PML-3 into the nuclear bodies and is activated after irradiation with ultraviolet. Antisense inhibition of HIPK2 expression reduces the ultraviolet-induced apoptosis. Furthermore, HIPK2 and p53 cooperate in the activation of p53-dependent transcription and apoptotic pathways. These data define a new functional interaction between p53 and HIPK2 that results in the targeted subcellular localization of p53 and initiation of apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics*
  • Apoptosis / radiation effects
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Carrier Proteins / radiation effects
  • Cell Nucleus / genetics
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Enzyme Activation / radiation effects
  • Genes, Tumor Suppressor
  • Humans
  • Mice
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Nuclear Proteins*
  • Oligonucleotides, Antisense
  • Phosphorylation
  • Promyelocytic Leukemia Protein
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Protein-Serine-Threonine Kinases / radiation effects
  • Serine
  • Transcription Factors / genetics
  • Transcription Factors / metabolism
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / metabolism*
  • Tumor Suppressor Proteins
  • Ultraviolet Rays

Substances

  • Carrier Proteins
  • Neoplasm Proteins
  • Nuclear Proteins
  • Oligonucleotides, Antisense
  • Pml protein, mouse
  • Promyelocytic Leukemia Protein
  • Protein Isoforms
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
  • PML protein, human
  • Serine
  • HIPK2 protein, human
  • Hipk2 protein, mouse
  • Protein-Serine-Threonine Kinases