Montano, Giorgia
(2013)
Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis.
[Tesi di dottorato]
| Item Type: |
Tesi di dottorato
|
| Lingua: |
English |
| Title: |
Role of WT1-ZNF224 interaction in the regulation of leukemia cells apoptosis |
| Creators: |
| Creators | Email |
|---|
| Montano, Giorgia | giorgia.montano@unina.it |
|
| 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: |
| nome | email |
|---|
| Arcari, Paolo | UNSPECIFIED |
|
| Tutor: |
| nome | email |
|---|
| Costanzo, Paola | paola.costanzo@unina.it |
|
| 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 |
[error in script]
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| Date Deposited: |
10 Apr 2013 15:51 |
| Last Modified: |
15 Jul 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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