Role of WT1-ZNF224 interaction in the expression of apoptosis-regulating genes.
The transcription factor Wilms' tumor 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 transactivation 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.
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
Giorgia
G
Montano
Elena
E
Cesaro
Luigi
L
Fattore
Karina
K
Vidovic
Chiara
C
Palladino
Rossella
R
Crescitelli
Paola
P
Izzo
Maria Caterina
MC
Turco
Paola
P
Costanzo
D017209:Apoptosis / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D003561:Cytarabine / Q000009:adverse effects; D004249:DNA Damage; D004268:DNA-Binding Proteins; D063185:Epigenetic Repression; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006801:Humans; D020014:K562 Cells; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation; D025721:WT1 Proteins / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D012097:Repressor Proteins; D014157:Transcription Factors; D025721:WT1 Proteins; C583751:WT1 protein, human; C470003:ZNF224 protein, human; D003561:Cytarabine