Suppression of the STK15 oncogenic activity requires a transactivation-independent p53 function.
Using a transactivation-defective p53 derivative as bait, STK15, a centrosome-associated oncogenic serine/threonine kinase, was isolated as a p53 partner. The p53-STK15 interaction was confirmed further by co-immunoprecipitation and GST pull-down studies. In co-transfection experiments, p53 suppressed STK15-induced centrosome amplification and cellular transformation in a transactivation-independent manner. The suppression of STK15 oncogenic activity by p53 might be explained in part by the finding that p53 inhibited STK15 kinase activity via direct interaction with the latter's Aurora box. Taken together, these findings revealed a novel mechanism for the tumor suppressor function of p53.
Chen
Shih-Shun
SS
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
Chang
Pi-Chu
PC
Cheng
Yu-Wen
YW
Tang
Fen-Mei
FM
Lin
Young-Sun
YS
D016475:3T3 Cells; D000818:Animals; D064096:Aurora Kinase A; D064127:Aurora Kinases; D001665:Binding Sites; D018385:Centrosome / Q000201:enzymology / Q000502:physiology; D017930:Genes, Reporter; D016158:Genes, p53; D006801:Humans; D020014:K562 Cells / Q000201:enzymology; D051379:Mice; D015513:Oncogene Proteins / Q000037:antagonists & inhibitors; D025941:Protein Interaction Mapping; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D017434:Protein Structure, Tertiary; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000502:physiology*; D020798:Two-Hybrid System Techniques
D015513:Oncogene Proteins; D011993:Recombinant Fusion Proteins; D016159:Tumor Suppressor Protein p53; C576917:AURKA protein, human; D064096:Aurora Kinase A; D064127:Aurora Kinases; D017346:Protein Serine-Threonine Kinases