Role of WT1-ZNF224 interaction in the expression of apoptosis-regulating genes

Research output: Contribution to journalArticle

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 Krppel-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 WT1ZNF224 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.

Details

Authors
  • Giorgia Montano
  • Elena Cesaro
  • Luigi Fattore
  • Karina Vidovic
  • Chiara Palladino
  • Rossella Crescitelli
  • Paola Izzo
  • Maria Caterina Turco
  • Paola Costanzo
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Medical Genetics
Original languageEnglish
Pages (from-to)1771-1782
JournalHuman Molecular Genetics
Volume22
Issue number9
Publication statusPublished - 2013
Publication categoryResearch
Peer-reviewedYes