Montano, Giorgia (2013) Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis. [Tesi di dottorato]
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Tesi G. Montano 30-3-13.pdf Download (2MB) | Anteprima |
| Tipologia del documento: | Tesi di dottorato |
|---|---|
| Lingua: | English |
| Titolo: | Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis |
| Autori: | Autore Email Montano, Giorgia giorgia.montano@unina.it |
| Data: | 30 Marzo 2013 |
| Numero di pagine: | 69 |
| Istituzione: | Università degli Studi di Napoli Federico II |
| Dipartimento: | 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: | nome email Arcari, Paolo [non definito] |
| Tutor: | nome email Costanzo, Paola paola.costanzo@unina.it |
| Data: | 30 Marzo 2013 |
| Numero di pagine: | 69 |
| Parole chiave: | Transcriptional factor interaction, apoptosis regulating genes. |
| Settori scientifico-disciplinari del MIUR: | Area 05 - Scienze biologiche > BIO/10 - Biochimica |
| Depositato il: | 10 Apr 2013 15:51 |
| Ultima modifica: | 15 Lug 2014 13:37 |
| URI: | http://www.fedoa.unina.it/id/eprint/9263 |
| DOI: | 10.6092/UNINA/FEDOA/9263 |
Abstract
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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