Characterization of the novel E3 ubiquitin ligase encoded in exon 3 of herpes simplex virus-1-infected cell protein 0
AUTOR(ES)
Hagglund, Ryan
FONTE
The National Academy of Sciences
RESUMO
Infected cell protein 0 (ICP0) of herpes simplex virus-1 is a 775-aa residue multifunctional protein that acts as a promiscuous transactivator linked to the degradation of several proteins. ICP0 is the only protein known which encodes two physically separated E3 ubiquitin (Ub) ligase domains, one, designated herpes virus Ub ligase 1 (HUL-1) located in a domain encoded in exon 3 and one designated herpes virus Ub ligase 2 (HUL-2) associated with the really interesting new gene (RING) finger domain encoded by exon 2. We report the following: (i) ICP0 residues 543–680 are sufficient for HUL-1 E3 activity and necessary determinants are encoded between residues 616 and 680. (ii) In substrate independent in vitro ubiquitylation reactions, a chimeric protein containing the HUL-1 domain promotes the ubiquitylation of itself and the ubiquitin conjugating enzyme (E2) cdc34 and interacts with cdc34. (iii) The mechanism of HUL-1 E3 function does not involve formation of a thioester between the HUL-1 domain and Ub. (iv) Residues 621–625 are essential for in vitro HUL-1 E3 activity and interaction between the HUL-1 domain and cdc34, suggesting that this interaction is required for HUL-1 E3 function.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=122990Documentos Relacionados
- Herpes simplex virus 1-infected cell protein 0 contains two E3 ubiquitin ligase sites specific for different E2 ubiquitin-conjugating enzymes
- The infected cell protein 0 of herpes simplex virus 1 dynamically interacts with proteasomes, binds and activates the cdc34 E2 ubiquitin-conjugating enzyme, and possesses in vitro E3 ubiquitin ligase activity
- Herpes Simplex Virus Type 1 Immediate-Early Protein ICP0 and Its Isolated RING Finger Domain Act as Ubiquitin E3 Ligases In Vitro
- Herpes Simplex Virus 1 Mutant in Which the ICP0 HUL-1 E3 Ubiquitin Ligase Site Is Disrupted Stabilizes cdc34 but Degrades D-Type Cyclins and Exhibits Diminished Neurotoxicity
- Requirements for the Nuclear-Cytoplasmic Translocation of Infected-Cell Protein 0 of Herpes Simplex Virus 1
