Novel homeodomain-interacting protein kinase family member, HIPK4, phosphorylates human p53 at serine 9

FEBS Lett. 2007 Dec 11;581(29):5649-57. doi: 10.1016/j.febslet.2007.11.022. Epub 2007 Nov 20.

Abstract

We describe here the cloning and characterization of a novel mouse homeodomain-interacting protein kinase (HIPK)-like gene, Hipk4. Hipk4 is expressed in lung and in white adipose tissue and encodes a 616 amino acid protein that includes a serine/threonine kinase domain. We demonstrate that HIPK4 could phosphorylate human p53 protein at serine 9, both in vitro and in vivo. Among known p53-responsive promoters, activity of the human survivin promoter, which is repressed by p53, was decreased by HIPK4 in p53 functional A549 cells. Human BCL2-associated X protein-promoter activity was not affected. These findings suggest that phosphorylation of p53 at serine 9 is important for p53 mediated transcriptional repression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Catalysis
  • Cell Differentiation
  • Cell Proliferation
  • Cloning, Molecular
  • DNA, Complementary / metabolism
  • Humans
  • Inhibitor of Apoptosis Proteins
  • Mice
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism
  • Molecular Sequence Data
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Promoter Regions, Genetic
  • Protein Serine-Threonine Kinases / analysis
  • Protein Serine-Threonine Kinases / genetics
  • Protein Serine-Threonine Kinases / metabolism*
  • Sequence Alignment
  • Serine / genetics
  • Serine / metabolism*
  • Survivin
  • Tumor Suppressor Protein p53 / metabolism*
  • bcl-2-Associated X Protein / genetics
  • bcl-2-Associated X Protein / metabolism

Substances

  • BAX protein, human
  • BIRC5 protein, human
  • DNA, Complementary
  • Inhibitor of Apoptosis Proteins
  • Microtubule-Associated Proteins
  • Neoplasm Proteins
  • Survivin
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Serine
  • HIPK4 protein, human
  • Protein Serine-Threonine Kinases