title: Herpes simplex virus immediate-early protein ICP0 is targeted by SIAH-1 for proteasomal degradation.
abstract: Herpes simplex virus (HSV) immediate-early protein ICP0 is a transcriptional activator with E3 ubiquitin ligase activity that induces the degradation of ND10 proteins, including the promyelocytic leukemia protein (PML) and Sp100. Moreover, ICP0 has a role in the derepression of viral genomes and in the modulation of the host interferon response to virus infection. Here, we report that ICP0 interacts with SIAH-1, a cellular E3 ubiquitin ligase that is involved in multiple cellular pathways and is itself capable of mediating PML degradation. This novel virus-host interaction profoundly stabilized SIAH-1 and recruited this cellular E3 ligase into ICP0-containing nuclear bodies. Moreover, SIAH-1 mediated the polyubiquitination of HSV ICP0 in vitro and in vivo. After infection of SIAH-1 knockdown cells with HSV, higher levels of ICP0 were produced, ICP0 was less ubiquitinated, and the half-life of this multifunctional viral regulatory protein was increased. These results indicate an inhibitory role of SIAH-1 during lytic infection by targeting ICP0 for proteasomal degradation.
authors.affiliation: Heinrich Pette Institute-Leibniz Institute for Experimental Virology, Martinistrasse 52, 20251 Hamburg, Germany.
authors.forename: Claus-Henning
authors.initials: CH
authors.lastname: Nagel
authors.forename: Nina
authors.initials: N
authors.lastname: Albrecht
authors.forename: Kristijana
authors.initials: K
authors.lastname: Milovic-Holm
authors.forename: Lakshmikanth
authors.initials: L
authors.lastname: Mariyanna
authors.forename: Britta
authors.initials: B
authors.lastname: Keyser
authors.forename: Bettina
authors.initials: B
authors.lastname: Abel
authors.forename: Britta
authors.initials: B
authors.lastname: Weseloh
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Hofmann
authors.forename: Martha M
authors.initials: MM
authors.lastname: Eibl
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
mesh_terms: D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D054884:Host-Pathogen Interactions; D006801:Humans; D006868:Hydrolysis; D017874:Immediate-Early Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D054875:Ubiquitination; D000098563:Seven in Absentia Proteins
chemical_list: D017931:DNA Primers; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C051804:Vmw110 protein, Human herpesvirus 1; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex