Physical and functional interaction between the HCMV IE2 protein and the Wilms' tumor suppressor WT1.
Human cytomegalovirus (HCMV) is a major renal pathogen in congenitally infected infants and renal allograft recipients. It has been shown that human kidney cells of glomerular, tubular, and vascular origin were all infected by HCMV in vitro. It has previously been demonstrated that the IE2 protein of HCMV directly associates with the zinc finger domain of Egr-1. The zinc finger region of WT1 is a sequence-specific DNA-binding domain which also recognizes the consensus DNA binding site (5'-CGCCCCCGC-3') of Egr-1, thus suggesting a possible interaction between WT1 and IE2. Here we demonstrate that HCMV IE2 binds to the C-terminal region of WT1 containing zinc finger domain in vivo as well as in vitro and that WT1 can inhibit IE2-driven transactivation of the responsive promoter. Our results suggest that WT1 may be able to regulate the functional activity of HCMV IE2. Furthermore, these data may provide new insights into the possible involvement of HCMV in WT1-related pathogeneses.
Kim
J M
JM
Institute for Molecular Biology, Seoul National University, Seoul, 151-742, Korea.
Hong
Y
Y
Semba
K
K
Kim
S
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D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular; D006224:Cricetinae; D004268:DNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D004926:Escherichia coli; D016147:Genes, Tumor Suppressor; D006801:Humans; D017874:Immediate-Early Proteins / Q000737:chemistry* / Q000378:metabolism*; D007668:Kidney; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor / Q000235:genetics; D011401:Promoter Regions, Genetic; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry* / Q000378:metabolism*; D014162:Transfection; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D025721:WT1 Proteins; D016335:Zinc Fingers
D004268:DNA-Binding Proteins; C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D008562:Membrane Glycoproteins; D010982:Platelet-Derived Growth Factor; D011993:Recombinant Fusion Proteins; D015534:Trans-Activators; D014157:Transcription Factors; C077406:UL115 protein, Human herpesvirus 5; D014759:Viral Envelope Proteins; D014764:Viral Proteins; D025721:WT1 Proteins; C071440:glycoprotein H, Cytomegalovirus; C499358:glycoprotein H, Human cytomegalovirus; C439068:glycoprotein O, cytomegalovirus