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Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms
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Dr Colin Miles
Florio F, Cesaro E, Montano G, Izzo P, Miles C, Costanzo P
Human Molecular Genetics
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Wilms' tumour suppressor gene, WT1, is mutated/deleted in ~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 (ZF) 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 ZF 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 subcellular 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.
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