A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK

Biochem Biophys Res Commun. 2006 May 26;344(1):377-85. doi: 10.1016/j.bbrc.2006.03.071. Epub 2006 Mar 22.

Abstract

PRPK phosphorylates serine-15 residue of p53 and enhances transcriptional activity. PRPK possesses a bipartite nuclear localization signal and localizes in nucleus when over-expressed in cells. However, intrinsic PRPK localizes mainly in the cytosol in situ. While studying the mechanisms in the distribution of intrinsic PRPK, we identified a PRPK binding protein, an ubiquitously expressed Small Ras-like GTPase, Rab1c, also named Ray or Rab35. The over-expressed Ray was distributed in the nucleus, cytosol, and cell membrane. Both Ray wild type and GTP-restrictively binding mutant Ray-Q67L, but not guanine nucleotide unstable binding mutant Ray-N120I, partially distributed the over-expressed PRPK to the cytosol and also suppressed the PRPK-induced p53-transcriptional activity profoundly. A Small Ras-like GTPase protein Ray was thus indicated to modulate p53 transcriptional activity of PRPK.

MeSH terms

  • Amino Acid Sequence
  • Cell Nucleus / chemistry
  • Cell Nucleus / metabolism*
  • Cytosol / chemistry
  • Cytosol / metabolism
  • GTP-Binding Proteins / analysis
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • Gene Expression Regulation
  • HeLa Cells
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Mutation
  • Oxidative Stress
  • Protein Kinases / analysis
  • Protein Kinases / metabolism*
  • Protein-Serine-Threonine Kinases
  • Transcription Factors / antagonists & inhibitors*
  • Transcription Factors / metabolism
  • Transcription, Genetic
  • Tumor Suppressor Protein p53 / antagonists & inhibitors*
  • Tumor Suppressor Protein p53 / metabolism
  • rab GTP-Binding Proteins

Substances

  • Intracellular Signaling Peptides and Proteins
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Protein Kinases
  • Protein-Serine-Threonine Kinases
  • TP53RK protein, human
  • GTP-Binding Proteins
  • RAB35 protein, human
  • rab GTP-Binding Proteins