P53 mutants suppress ZBP-89 function.
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.


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.


CONCLUSIONS
ZBP-89 is an important co-activator of wild-type p53 and both proteins are negatively affected by functionally inactive p53 mutants.
Okada
Morihiro
M
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-2200, USA.
Tessier
Arthur
A
Bai
Longchuan
L
Merchant
Juanita L
JL
D000818:Animals; D003110:Colonic Neoplasms / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D016158:Genes, p53; D045325:HCT116 Cells; D006801:Humans; D017354:Point Mutation; D051381:Rats; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*; D015533:Transcriptional Activation; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D004268:DNA-Binding Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C110951:ZNF148 protein, human