Jab1 has negative effects on p53-mediated genotoxic stresses.
In this study, we use promoter analysis to show that interaction between Jab1 and p53 induces suppression of p53 activation in U2OS and H1299 cells. Interaction between p53 and Jab1 was further confirmed by immunoprecipitation and immunofluorescent analyses. In particular, Jab1 was able to induce nuclear export of p53 as previously reported. When Jab1 was overexpressed in U2OS cells followed by etoposide or hydrogen peroxide (H(2)O(2)), cell death induced by such stresses was protected against. On the contrary, when the level of Jab1 was suppressed in U2OS cells, cytotoxicity imposed by etoposide and H(2)O(2) was dramatically increased, suggesting a cell protective role for Jab1. These results indicate that Jab1 is a negative regulator of p53 and a plausible oncogene.
Lee
Eun-Woo
EW
Department of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon 440-746, Korea.
Lee
Sangsik
S
Song
Jaewhan
J
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000972:Antineoplastic Agents, Phytogenic / Q000378:metabolism; D000075686:COP9 Signalosome Complex; D016923:Cell Death / Q000502:physiology; D045744:Cell Line, Tumor; D004249:DNA Damage; D005047:Etoposide / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D016877:Oxidants / Q000378:metabolism; D010447:Peptide Hydrolases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*
D000972:Antineoplastic Agents, Phytogenic; D047908:Intracellular Signaling Peptides and Proteins; D016877:Oxidants; D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D006861:Hydrogen Peroxide; D010447:Peptide Hydrolases; C501488:COPS5 protein, human; D000075686:COP9 Signalosome Complex