A Small Ras-like protein Ray/Rab1c modulates the p53-regulating activity of PRPK.
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.
Abe
Yasuhito
Y
Department of Pathology, Division of Molecular Pathology, National University Corporation, Ehime University School of Medicine, Toh-on, Ehime 791-0295, Japan. yasuhito@m.ehime-u.ac.jp
Takeuchi
Takashi
T
Imai
Yoshinori
Y
Murase
Ryuichi
R
Kamei
Yoshiaki
Y
Fujibuchi
Taketsugu
T
Matsumoto
Suguru
S
Ueda
Norifumi
N
Ogasawara
Masahito
M
Shigemoto
Kazuhiro
K
Kito
Katsumi
K
D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009154:Mutation; D018384:Oxidative Stress; D011494:Protein Kinases / Q000032:analysis / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D014157:Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic; D016159:Tumor Suppressor Protein p53 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020691:rab GTP-Binding Proteins
D047908:Intracellular Signaling Peptides and Proteins; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C441644:TP53RK protein, human; D019204:GTP-Binding Proteins; C511183:RAB35 protein, human; D020691:rab GTP-Binding Proteins