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.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.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.ZBP-89 is an important co-activator of wild-type p53 and both proteins are negatively affected by functionally inactive p53 mutants.