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

Montano, Giorgia ; Cesaro, Elena ; Fattore, Luigi ; Vidovic, Karina LU ; Palladino, Chiara ; Crescitelli, Rossella ; Izzo, Paola ; Turco, Maria Caterina and Costanzo, Paola (2013) In Human Molecular Genetics 22(9). p.1771-1782
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... (More)
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. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
22
issue
9
pages
1771 - 1782
publisher
Oxford University Press
external identifiers
  • wos:000317431100007
  • scopus:84875922689
  • pmid:23362234
ISSN
0964-6906
DOI
10.1093/hmg/ddt027
language
English
LU publication?
yes
id
2f762335-294e-4e76-acb5-62a1fbc04639 (old id 3738981)
date added to LUP
2016-04-01 10:46:34
date last changed
2022-02-10 05:49:04
@article{2f762335-294e-4e76-acb5-62a1fbc04639,
  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.}},
  author       = {{Montano, Giorgia and Cesaro, Elena and Fattore, Luigi and Vidovic, Karina and Palladino, Chiara and Crescitelli, Rossella and Izzo, Paola and Turco, Maria Caterina and Costanzo, Paola}},
  issn         = {{0964-6906}},
  language     = {{eng}},
  number       = {{9}},
  pages        = {{1771--1782}},
  publisher    = {{Oxford University Press}},
  series       = {{Human Molecular Genetics}},
  title        = {{Role of WT1-ZNF224 interaction in the expression of apoptosis-regulating genes}},
  url          = {{http://dx.doi.org/10.1093/hmg/ddt027}},
  doi          = {{10.1093/hmg/ddt027}},
  volume       = {{22}},
  year         = {{2013}},
}