SIAH-1 interacts with the Kaposi's sarcoma-associated herpesvirus-encoded ORF45 protein and promotes its ubiquitylation and proteasomal degradation.
Kaposi's sarcoma-associated herpesvirus (KSHV), also referred to as human herpesvirus 8, is a potentially tumorigenic virus implicated in the etiology of Kaposi's sarcoma, primary effusion lymphoma, and some forms of multicentric Castleman's disease. The open reading frame 45 (ORF45) protein, encoded by the KSHV genome, is capable of inhibiting virus-dependent interferon induction and appears to be essential for both early and late stages of infection. In the present study, we show, both in yeast two-hybrid assays and in mammalian cells, that the ORF45 protein interacts with the cellular ubiquitin E3 ligase family designated seven in absentia homologue (SIAH). We provide evidence that SIAH-1 promotes the degradation of KSHV ORF45 through a RING domain-dependent mechanism and via the ubiquitin-proteasome system. Furthermore, our data indicate the involvement of SIAH-1 in the regulation of the expression of ORF45 in KSHV-infected cells. Since the availability of KSHV ORF45 is expected to influence the course of KSHV infection, our findings identify a novel biological role for SIAH proteins as modulators of virus infection.
Abada
Rinat
R
The Mina and Everard Goodman Faculty of Life Sciences, Bar Ilan University, Ramat-Gan, Israel.
Dreyfuss-Grossman
Tsofia
T
Herman-Bachinsky
Yifat
Y
Geva
Haim
H
Masa
Shiri-Rivka
SR
Sarid
Ronit
R
D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D006868:Hydrolysis; D017874:Immediate-Early Proteins / Q000378:metabolism*; D047468:Immunoprecipitation; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D011485:Protein Binding; D025801:Ubiquitin / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*; D000098563:Seven in Absentia Proteins
D017931:DNA Primers; D017874:Immediate-Early Proteins; D009687:Nuclear Proteins; C456286:ORF45 protein, Kaposi's sarcoma-associated herpesvirus; D025801:Ubiquitin; D014764:Viral Proteins; D044767:Ubiquitin-Protein Ligases; D000098563:Seven in Absentia Proteins; D046988:Proteasome Endopeptidase Complex