Montano, Giorgia (2013) Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis. [Tesi di dottorato]

Tesi G. Montano 30-3-13.pdf

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Item Type: Tesi di dottorato
Lingua: English
Title: Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis
Date: 30 March 2013
Number of Pages: 69
Institution: Università degli Studi di Napoli Federico II
Department: Medicina Molecolare e Biotecnologie Mediche
Scuola di dottorato: Scienze biologiche
Dottorato: Biochimica e biologia cellulare e molecolare
Ciclo di dottorato: 25
Coordinatore del Corso di dottorato:
Date: 30 March 2013
Number of Pages: 69
Uncontrolled Keywords: Transcriptional factor interaction, apoptosis regulating genes.
Settori scientifico-disciplinari del MIUR: Area 05 - Scienze biologiche > BIO/10 - Biochimica
Date Deposited: 10 Apr 2013 15:51
Last Modified: 15 Jul 2014 13:37
DOI: 10.6092/UNINA/FEDOA/9263


The transcription factor Wilms’ tumour 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 trans-activation 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.


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