P53 mutants suppress ZBP-89 function.

Morihiro Okada; Arthur Tessier; Longchuan Bai; Juanita L Merchant

PubMed · 16827139

P53 mutants suppress ZBP-89 function.

Morihiro Okada·Arthur Tessier·Longchuan Bai·Juanita L Merchant

Abstract

BACKGROUND: ZBP-89 is a widely expressed Krüppel-type zinc finger transcription factor that binds to GC-rich elements and represses or activates known target genes. ZBP-89 stabilizes wild-type p53 and can induce apoptosis independently of p53. Tissues with p53 mutations are predisposed to transformation and are more resistant to chemotherapy. MATERIALS AND METHODS: The effect of ZBP-89 on seven sporadic p53 mutants was investigated. It was then examined whether a cell null for p53 in comparison to one expressing mutated p53 is more sensitive or resistant to chemotherapy in the presence of increased levels of ZBP-89. RESULTS: None of the p53 mutations were stabilized by ZBP-89 except for the A161T p53 mutation, which exhibited constitutive transcriptional activity. ZBP-89 potentiated p53-mediated cell death with 10 nM staurosporine and 100 nM etoposide, but did not in the presence of the R273H p53 mutation. CONCLUSION: ZBP-89 is an important co-activator of wild-type p53 and both proteins are negatively affected by functionally inactive p53 mutants.

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Animals Colonic Neoplasms DNA-Binding Proteins Genes, p53 HCT116 Cells Humans Point Mutation Rats Transcription Factors Transcriptional Activation Transfection Tumor Suppressor Protein p53 Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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Morihiro Okada, Arthur Tessier, Longchuan Bai, Juanita L Merchant. P53 mutants suppress ZBP-89 function.. https://pubmed.ncbi.nlm.nih.gov/16827139/

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