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| Restoration of the transcription activation function to mutant p53 in human cancer cells |
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| Author(s): Abarzua P, LoSardo JE, Gubler ML, Spathis R, Lu YA, Felix A, Neri A |
| Source: ONCOGENE Volume: 13 Issue: 11 Pages: 2477-2482 Published: DEC 5 1996 |
| Times Cited: 60 References: 48 |
| Abstract: The p53 tumor suppressor gene product is a sequence-specific transcription activator frequently mutated in a variety of human malignancies. Typically, tumor-derived p53 missense mutants are defective in DNA binding and this is likely to result in a failure to active p53-regulated genes. Hence, restoring function to mutant p53 represents an attractive target to develop a novel cancer chemotherapeutic agent. We now show that a small chemically modified peptide derived from p53 restores sequence-specific DNA binding to a subset of p53 mutants. Moreover, when microinjected into human colon carcinoma cells this peptide restores the transcription activation function to endogenous mutant p53 protein. This is the first example showing that a small peptide molecule can reverse the effect of several inactivating missense mutations and restore protein function. |
| Document Type: Article |
| Language: English |
| Reprint Address: Abarzua, P (reprint author), HOFFMANN LA ROCHE INC, ROCHE RES CTR, NUTLEY, NJ 07110 USA |
| Publisher: STOCKTON PRESS, HOUNDMILLS, BASINGSTOKE, HAMPSHIRE, ENGLAND RG21 6XS |
| Subject Category: Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity |
| IDS Number: VX108 |
| ISSN: 0950-9232 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |