Expression of a mutant p193/CUL7 molecule confers resistance to MG132- and etoposide-induced apoptosis independent of p53 or Parc binding.
p193/CUL7 is an E3 ubiquitin ligase initially identified as an SV40 Large T Antigen binding protein. Expression of a dominant interfering variant of mouse p193/CUL7 (designated 1152stop) conferred resistance to MG132- and etoposide-induced apoptosis in U2OS cells. Immune precipitation/Western analyses revealed that endogenous p193/CUL7 formed a complex with Parc (a recently identified parkin-like ubiquitin ligase) and p53. Apoptosis resistance did not result from 1152stop-mediated disruption of the endogenous p193/CUL7 binding partners. Moreover, 1152stop molecule did not directly bind to endogenous p193/CUL7, Parc or p53. These data suggested a role for p193/CUL7 in the regulation of apoptosis independently of p53 and Parc activity.
Dowell
Joshua D
JD
Wells Center for Pediatric Research, Division of Pediatric Cardiology and Krannert Institute of Cardiology, Indiana University School of Medicine, Indianapolis, IN 46202-5225, USA.
Tsai
Shih-Chong
SC
Dias-Santagata
Dora C
DC
Nakajima
Hidehiro
H
Wang
Zhuo
Z
Zhu
Wuqiang
W
Field
Loren J
LJ
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D044842:Cullin Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D027101:DNA Topoisomerase IV / Q000378:metabolism; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects; D005047:Etoposide / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology*; D051379:Mice; D009154:Mutation / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D061988:Proteasome Inhibitors; D011485:Protein Binding; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; C494817:Cul7 protein, mouse; D044842:Cullin Proteins; D007976:Leupeptins; D061988:Proteasome Inhibitors; D016159:Tumor Suppressor Protein p53; D005047:Etoposide; D046988:Proteasome Endopeptidase Complex; D027101:DNA Topoisomerase IV; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde