The Wilms’ tumour suppressor gene, WT1, is mutated/deleted in approximately 15% of Wilms’ tumours, highly expressed in the majority of other cancers and is essential for normal embryonic development. The gene encodes multiple isoforms of a zinc-finger protein with diverse cellular functions, in particular participating in both transcriptional and post-transcriptional gene regulation. Physical interactions of other cellular proteins with WT1 are known to modulate its function. However, despite the isolation of several WT1-binding proteins, the mechanisms involved in regulating WT1 activities are not clearly understood. In this study we report the identification of the Krüppel-like zinc finger protein, ZNF224, as a novel human WT1-associating protein and demonstrate that ZNF224 and its isoform ZNF255 show a specific pattern of interaction with the WT1 splicing variants WT1(-KTS) and WT1(+KTS). These interactions occur in different sub-cellular compartments and are devoted to control different cellular pathways. The nuclear interaction between ZNF224 and WT1(-KTS) results in an increase in trascriptional activation mediated by WT1, implying that ZNF224 acts as a co-regulator of WT1, whereas, on the contrary, the results obtained for ZNF255 suggest a role for this protein in RNA processing together with WT1. Moreover, our data give the first functional information about the involvement of ZNF255 in a specific molecular pathway, RNA maturation and processing.

Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms / Florio, F; Cesaro, Elena; Montano, Giorgia; Izzo, Paola; Miles, C; Costanzo, Paola. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 19:18(2010), pp. 3544-3556. [10.1093/hmg/ddq270]

Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms.

CESARO, Elena;MONTANO, GIORGIA;IZZO, PAOLA;COSTANZO, PAOLA
2010

Abstract

The Wilms’ tumour suppressor gene, WT1, is mutated/deleted in approximately 15% of Wilms’ tumours, highly expressed in the majority of other cancers and is essential for normal embryonic development. The gene encodes multiple isoforms of a zinc-finger protein with diverse cellular functions, in particular participating in both transcriptional and post-transcriptional gene regulation. Physical interactions of other cellular proteins with WT1 are known to modulate its function. However, despite the isolation of several WT1-binding proteins, the mechanisms involved in regulating WT1 activities are not clearly understood. In this study we report the identification of the Krüppel-like zinc finger protein, ZNF224, as a novel human WT1-associating protein and demonstrate that ZNF224 and its isoform ZNF255 show a specific pattern of interaction with the WT1 splicing variants WT1(-KTS) and WT1(+KTS). These interactions occur in different sub-cellular compartments and are devoted to control different cellular pathways. The nuclear interaction between ZNF224 and WT1(-KTS) results in an increase in trascriptional activation mediated by WT1, implying that ZNF224 acts as a co-regulator of WT1, whereas, on the contrary, the results obtained for ZNF255 suggest a role for this protein in RNA processing together with WT1. Moreover, our data give the first functional information about the involvement of ZNF255 in a specific molecular pathway, RNA maturation and processing.
2010
Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms / Florio, F; Cesaro, Elena; Montano, Giorgia; Izzo, Paola; Miles, C; Costanzo, Paola. - In: HUMAN MOLECULAR GENETICS. - ISSN 0964-6906. - 19:18(2010), pp. 3544-3556. [10.1093/hmg/ddq270]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/370431
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