Microinjection of monoclonal antibody PAb421 into human SW480 colorectal carcinoma cells restores the transcription activation function to mutant p53.
The p53 tumor suppressor is a transcription factor frequently mutated in human malignancies. Tumor-derived p53 missense mutants are defective in sequence-specific DNA binding and fail to activate p53 target genes. mAb PAb421 was shown previously to restore DNA binding to selected p53 mutants in vitro. Here we show that mAb PAb421 when microinjected into human SW480 colorectal carcinoma cells restores the transcription activation function to the resident mutant p53 (arg to his 273, pro to ser 309). Codon 273 is the second most frequent p53 missense mutant found in human tumors. Our results lend support to the concept of restoring wild-type function to mutant p53 as a strategy for cancer therapy.
Abarzúa
P
P
Department of Oncology, Roche Research Center, Hoffmann-LaRoche Inc., Nutley, New Jersey 07110, USA.
LoSardo
J E
JE
Gubler
M L
ML
Neri
A
A
D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D001483:Base Sequence; D001665:Binding Sites; D002277:Carcinoma / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53; D066298:In Vitro Techniques; D008175:Lung Neoplasms / Q000235:genetics; D008845:Microinjections; D008969:Molecular Sequence Data; D009154:Mutation; D009838:Oligodeoxyribonucleotides / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D000911:Antibodies, Monoclonal; D004268:DNA-Binding Proteins; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53