Role of wt1-znf224 interaction in the expression of apoptosis-regulating genes

Giorgia Montano, Elena Cesaro, Luigi Fattore, Karina Vidovic, Chiara Palladino, Rossella Crescitelli, Paola Izzo, Maria Caterina Turco, Paola Costanzo

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Abstract

The transcription factor Wilms' tumor gene 1, WT1, is implicated both in normal developmental processes and in the generation of a variety of solid tumors and hematological malignancies. Physical interactions of other cellular proteins with WT1 are known to modulate its function. We previously identified the Krüppel-like zinc-finger protein, ZNF224, as a novel human WT1-associating protein that enhances the transcriptional activation of the human vitamin D receptor promoter by WT1. Here, we have analyzed the effects of WT1-ZNF224 interaction on the expression of apoptosis-regulating genes in the chronic myelogenous leukemia (CML) K562 cell line. The results demonstrated that ZNF224 acts in fine tuning of WT1-dependent control of gene expression, acting as a co-activator of WT1 in the regulation of proapoptotic genes and suppressing WT1 mediated transactivation of antiapoptotitc genes. Moreover, the DNA damaging drug cytosine arabinoside (ara-C) induces expression of ZNF224 in K562 cells and this induction enhances cell apoptotic response to ara-C. These findings suggest that ZNF224 can be a mediator of DNA damage-induced apoptosis in leukemia cells.

Original languageEnglish
Article numberddt027
Pages (from-to)1771-1782
Number of pages12
JournalHuman Molecular Genetics
Volume22
Issue number9
DOIs
Publication statusPublished - May 2013

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ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

Montano, G., Cesaro, E., Fattore, L., Vidovic, K., Palladino, C., Crescitelli, R., Izzo, P., Turco, M. C., & Costanzo, P. (2013). Role of wt1-znf224 interaction in the expression of apoptosis-regulating genes. Human Molecular Genetics, 22(9), 1771-1782. [ddt027]. https://doi.org/10.1093/hmg/ddt027