E3 ubiquitin-protein ligase ICP0 (EC 2.3.2.27) (Alpha-0 protein) (Immediate-early protein IE110) (RING-type E3 ubiquitin transferase ICP0) (Trans-acting transcriptional protein ICP0) (VMW110)

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MEPRPGASTRRPEGRPQREPAPDVWVFPCDRDLPDSSDSEAETEVGGRGDADHHDDDSASEADSTDTELFETGLLGPQGVDGGAVSGGSPPREEDPGSCG
GAPPREDGGSDEGDVCAVCTDEIAPHLRCDTFPCMHRFCIPCMKTWMQLRNTCPLCNAKLVYLIVGVTPSGSFSTIPIVNDPQTRMEAEEAVRAGTAVDF
IWTGNQRFAPRYLTLGGHTVRALSPTHPEPTTDEDDDDLDDADYVPPAPRRTPRAPPRRGAAAPPVTGGASHAAPQPAAARTAPPSAPIGPHGSSNTNTT
TNSSGGGGSRQSRAAAPRGASGPSGGVGVGVGVVEAEAGRPRGRTGPLVNRPAPLANNRDPIVISDSPPASPHRPPAAPMPGSAPRPGPPASAAASGPAR
PRAAVAPCVRAPPPGPGPRAPAPGAEPAARPADARRVPQSHSSLAQAANQEQSLCRARATVARGSGGPGVEGGHGPSRGAAPSGAAPLPSAASVEQEAAV
RPRKRRGSGQENPSPQSTRPPLAPAGAKRAATHPPSDSGPGGRGQGGPGTPLTSSAASASSSSASSSSAPTPAGAASSAAGAASSSASASSGGAVGALGG
RQEETSLGPRAASGPRGPRKCARKTRHAETSGAVPAGGLTRYLPISGVSSVVALSPYVNKTITGDCLPILDMETGNIGAYVVLVDQTGNMATRLRAAVPG
WSRRTLLPETAGNHVMPPEYPTAPASEWNSLWMTPVGNMLFDQGTLVGALDFRSLRSRHPWSGEQGASTRDEGKQ

Evades nuclear antiviral defenses triggered by dsDNA viruses. Acts during the initial stages of lytic infection and the reactivation of latent viral genome. Prevents the antiviral effect of nuclear bodies by degrading host PML and SP100. Prevents antiviral response to viral DNA induced by IFI16 by degrading it. Additionally, inhibits host IRF3 nuclear signaling to prevent interferon production by the infected cells. Interestingly, the E3 ubiquitin ligase activity associated with the RING finger domain does not seem to be directly required to inhibit the activation of IRF3 but instead plays a critical role in modulating the cellular localization of ICP0. Upon reactivation of latent genome, suppresses the silencing of viral DNA by dissociating either HDAC1 or HDAC2 from the HDAC-RCOR1-REST-KDM1A complex localized at the ND10 structures and causes their dispersal. Two cellular histone ubiquitin ligases RNF8 and RNF168 are also targeted by ICP0 for degradation, leading to a loss of ubiquitinated forms of H2A, a relief of transcriptional repression, and the activation of latent viral genomes. Enhances the localization of host CCND3 to ND10 bodies that serve as precursors of replication compartments to enable efficient viral replication. Like many RING-finger E3 ubiquitin ligases, ICP0 can induce its own ubiquitination, an activity that promotes its instability due to its targeting to the 26S proteasome for degradation. ICP0 restricts this process by recruiting the cellular ubiquitin-specific protease USP7 that cleaves the anchored ubiquitin chains from ICP0, thereby promoting its stabilization.

Host cytoplasm . Host nucleus .

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