PIAS1 enhances SUMO-1 modification and the transactivation activity of the major immediate-early IE2 protein of human cytomegalovirus.
The protein inhibitor of activated STAT1 (PIAS1), known to be a small ubiquitin-like modifier (SUMO) E3 ligase, was found to interact with the human cytomegalovirus IE2 protein. We found that the sumoylation of IE2 was markedly enhanced by wild-type PIAS1 but not by a mutant containing a Cys to Ser substitution at position 351 (C351S) within the RING finger-like domain. In target reporter gene assays, wild-type PIAS1, but not the C351S mutant, enhanced the IE2-mediated transactivations of viral polymerase promoter and cellular cyclin E promoter and this augmentation required the intact sumoylation sites of IE2. Our results suggest that PIAS1 acts as a SUMO E3 ligase toward IE2 and that it may regulate the transactivation function of IE2. To our knowledge, IE2 is the first viral target found to be regulated by a SUMO E3 ligase.
Lee
Jang-Mi
JM
Department of Molecular Cell Biology, Sungkyunkwan University, School of Medicine, Samsung Biomedical Research Institute, 300 Chunchundong, Jangangu, Kyonggido 440-746, South Korea.
Kang
Hee-Jung
HJ
Lee
Hye-Ra
HR
Choi
Cheol Yong
CY
Jang
Won-Jong
WJ
Ahn
Jin-Hyun
JH
D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D003587:Cytomegalovirus / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics / Q000378:metabolism; D005696:Galactosidases / Q000378:metabolism; D017930:Genes, Reporter / Q000235:genetics; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D050828:Protein Inhibitors of Activated STAT; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D025842:SUMO-1 Protein / Q000378:metabolism*; D015534:Trans-Activators / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
C069186:IE2 protein, Cytomegalovirus; D017874:Immediate-Early Proteins; D050828:Protein Inhibitors of Activated STAT; D011506:Proteins; D011993:Recombinant Fusion Proteins; D025842:SUMO-1 Protein; D015534:Trans-Activators; D044767:Ubiquitin-Protein Ligases; D004259:DNA-Directed DNA Polymerase; D005696:Galactosidases