Association of Ubc9, an E2 ligase for SUMO conjugation, with p53 is regulated by phosphorylation of p53.
Small ubiquitin-like modifier-1 (SUMO-1) conjugation to the tumor suppressor protein p53 seems to be regulated by murine double minute 2 homologue (Mdm2). It is thought that the physical association of Mdm2 with p53 is important for the enhancement of SUMO-1 conjugation to p53. However, mutant p53 that does not associate with Mdm2 is still sumoylated, albeit at a reduced level, suggesting that sumoylation of p53 is independent of the presence of Mdm2 and there is a direct association of ubiquitin-conjugating enzyme 9 (Ubc9), an E2 ligase for sumoylation, with p53. Here, we report evidence of the direct interaction of Ubc9 with p53. Furthermore, we observed that the interaction of Ubc9 with p53 was regulated by phosphorylation of p53. In particular, in cells treated with adriamycin that is a DNA damaging agent and that enhances phosphorylation of p53 at Ser-20, SUMO conjugation of p53 was severely impaired possibly by reduced affinity of Ubc9 to p53.
Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Jye-Yee
JY
Lin
Takayuki
T
Ohshima
Kunitada
K
Shimotohno
D002460:Cell Line; D004249:DNA Damage / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology; D006801:Humans; D009154:Mutation / Q000235:genetics; D010766:Phosphorylation / Q000187:drug effects; D011485:Protein Binding; D025842:SUMO-1 Protein / Q000235:genetics / Q000378:metabolism*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism*; D044763:Ubiquitin-Conjugating Enzymes / Q000235:genetics / Q000378:metabolism*; D000098843:Ubiquitin-Conjugating Enzyme UBC9
D025842:SUMO-1 Protein; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D044763:Ubiquitin-Conjugating Enzymes; D000098843:Ubiquitin-Conjugating Enzyme UBC9