title: The ribonucleotide reductase domain of the R1 subunit of herpes simplex virus type 2 ribonucleotide reductase is essential for R1 antiapoptotic function.
abstract: The R1 subunit (ICP10) of herpes simplex virus type 2 (HSV-2) ribonucleotide reductase (RR), which in addition to its C-terminal reductase domain possesses a unique N-terminal domain of about 400 aa, protects cells against apoptosis. As the NH(2) domain on its own is not antiapoptotic, it has been postulated that both domains of R1 or part(s) of them could be necessary for this function. Here, N- and C-terminal deletions were introduced in HSV-2 R1 to map the domain(s) involved in its antiapoptotic potential. The results showed that, whereas most of the NH(2) domain including part of the recently described putative alpha-crystallin domain is dispensable for antiapoptotic activity, it is the integrity of the structured RR domain that is required for protection. As the alpha-crystallin domain appears to play an important role in protein folding and oligomerization, the N-terminal boundary of the antiapoptotic domain could not be defined precisely. In addition, this study provided evidence that overexpression of HSV-2 R2 at levels up to 30-fold more than HSV-2 R1 did not decrease protection from tumour necrosis factor alpha, indicating that the R1 surface where R2 binds is not involved in antiapoptotic activity. Importantly, this result suggests that the co-expression of both RR subunits during the lytic cycle should not affect protection from this cytokine.
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Est, Montréal, QC H2L 4M1, Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Chabaud
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Est, Montréal, QC H2L 4M1, Canada.
authors.forename: A Marie-Josée
authors.initials: AM
authors.lastname: Sasseville
authors.affiliation: Institut de Recherche en Biotechnologie, 6100 ave Royalmount, Montréal, QC H4P 2R2, Canada.
authors.forename: Seyyed Mehdy
authors.initials: SM
authors.lastname: Elahi
authors.affiliation: Institut de Recherche en Biotechnologie, 6100 ave Royalmount, Montréal, QC H4P 2R2, Canada.
authors.forename: Antoine
authors.initials: A
authors.lastname: Caron
authors.affiliation: Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Est, Montréal, QC H2L 4M1, Canada.
authors.forename: Florent
authors.initials: F
authors.lastname: Dufour
authors.affiliation: INRS-IAF, Université du Québec, Laval, QC H7N 4Z3, Canada.|Département de Microbiologie et Immunologie, Université de Montréal, QC, Canada.|Institut de Recherche en Biotechnologie, 6100 ave Royalmount, Montréal, QC H4P 2R2, Canada.
authors.forename: Bernard
authors.initials: B
authors.lastname: Massie
authors.affiliation: Département de Médecine, Université de Montréal, QC, Canada.|Département de Microbiologie et Immunologie, Université de Montréal, QC, Canada.|Centre de Recherche du Centre Hospitalier de l'Université de Montréal and Institut du Cancer de Montréal, Hôpital Notre-Dame, 1560 Sherbrooke Est, Montréal, QC H2L 4M1, Canada.
authors.forename: Yves
authors.initials: Y
authors.lastname: Langelier
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D006367:HeLa Cells; D018258:Herpesvirus 2, Human / Q000201:enzymology* / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D009154:Mutation; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012264:Ribonucleotide Reductases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D014409:Tumor Necrosis Factor-alpha; C100671:ICP10 protein, herpes simplex virus type 2; D012264:Ribonucleotide Reductases; D017346:Protein Serine-Threonine Kinases