Biochemical and functional interaction between ZNF224 and ZNF255, two members of the Kruppel-like zinc-finger protein family and WT1 protein isoforms.
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 (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.
Florio
Francesca
F
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Napoli, Italy.
Cesaro
Elena
E
Montano
Giorgia
G
Izzo
Paola
P
Miles
Colin
C
Costanzo
Paola
P
D002460:Cell Line; D006801:Humans; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*; D009396:Wilms Tumor / Q000235:genetics / Q000378:metabolism
D020033:Protein Isoforms; D012097:Repressor Proteins; D025721:WT1 Proteins; C470003:ZNF224 protein, human