The small molecule 2-phenylethynesulfonamide induces covalent modification of p53.
p53 is a tumor suppressor protein which is either lost or inactivated in a large majority of tumors. The small molecule 2-phenylethynesulfonamide (PES) was originally identified as the inhibitor of p53 effects on the mitochondrial death pathway. In this report we demonstrate that p53 protein from PES-treated cells was detected in reduced mobility bands between molecular weights 95-220 kDa. Resolution of p53 aggregates on urea gel was unable to reduce the high molecular weight p53 aggregates, which were shown to be primarily located in the nucleus. Therefore, our data suggest that PES exerts its effects through covalent cross-linking and nuclear retention of p53.
Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, 2660 Oak St., Vancouver, BC, V6H 3Z6, Canada.
Sarwat
S
Jamil
Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, 2660 Oak St., Vancouver, BC, V6H 3Z6, Canada.
Payman
P
Hojabrpour
Department of Medicine, University of British Columbia and Vancouver Coastal Health Research Institute, 2660 Oak St., Vancouver, BC, V6H 3Z6, Canada. Electronic address: vduronio@mail.ubc.ca.
Vincent
V
Duronio
D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001665:Binding Sites / Q000187:drug effects; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism*; D003432:Cross-Linking Reagents / Q000008:administration & dosage / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008928:Mitochondria / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008970:Molecular Weight; D011485:Protein Binding / Q000187:drug effects; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000737:chemistry / Q000378:metabolism*
C545747:2-phenylacetylenesulfonamide; D003432:Cross-Linking Reagents; D013449:Sulfonamides; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53