WT1 gene is described to play an oncogenic role in a variety of tumours from different origins, including leukemias. In comparison to normal progenitor cells, it is overexpressed in acute lymphoblastic and myeloblastic leukemia, and in the blast crisis phase of chronic myelogenous leukaemia. Modulation of some members of the bcl-2 family has been associated with apoptosis inhibition by WT1. Among proteins that regulate apoptosis in leukemia cells, a role is assigned to BAG3, a member of the BAG family of co-chaperones. In this study we demonstrated that WT1 protein induces bag3 gene expression and that WT1- mediated increase in BAG3 protein levels contributes to the pro-survival role of WT1 in leukemic cells. The identification of bag3 as a target gene of WT1 improves our understanding of apoptosis regulation by this factor.

WT1 protein is a transcriptional activator of the antiapoptotic bag3 gene.

Cesaro E;IZZO, PAOLA;COSTANZO, PAOLA
2010

Abstract

WT1 gene is described to play an oncogenic role in a variety of tumours from different origins, including leukemias. In comparison to normal progenitor cells, it is overexpressed in acute lymphoblastic and myeloblastic leukemia, and in the blast crisis phase of chronic myelogenous leukaemia. Modulation of some members of the bcl-2 family has been associated with apoptosis inhibition by WT1. Among proteins that regulate apoptosis in leukemia cells, a role is assigned to BAG3, a member of the BAG family of co-chaperones. In this study we demonstrated that WT1 protein induces bag3 gene expression and that WT1- mediated increase in BAG3 protein levels contributes to the pro-survival role of WT1 in leukemic cells. The identification of bag3 as a target gene of WT1 improves our understanding of apoptosis regulation by this factor.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/370432
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