title: Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-κB activation.
abstract: Kaposi's sarcoma-associated herpesvirus (KSHV) has been linked to the development of Kaposi's sarcoma, primary effusion lymphoma, and multicentric Castleman's disease (MCD). We have characterized the role of KSHV-encoded viral FLICE inhibitory protein (vFLIP) K13 in the modulation of anti-IgM-induced growth arrest and apoptosis in B cells. We demonstrate that K13 protects WEHI 231, an immature B-cell line, against anti-IgM-induced growth arrest and apoptosis. The protective effect of K13 was associated with the activation of the NF-κB pathway and was deficient in a mutant K13 with three alanine substitutions at positions 58 to 60 (K13-58AAA) and a structural homolog, vFLIP E8, both of which lack NF-κB activity. K13 upregulated the expression of NF-κB subunit RelB and blocked the anti-IgM-induced decline in c-Myc and rise in p27(Kip1) that have been associated with growth arrest and apoptosis. K13 also upregulated the expression of Mcl-1, an antiapoptotic member of the Bcl2 family. Finally, K13 protected the mature B-cell line Ramos against anti-IgM-induced apoptosis through NF-κB activation. Inhibition of anti-IgM-induced apoptosis by K13 may contribute to the development of KSHV-associated lymphoproliferative disorders.
authors.affiliation: Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Keck School of Medicine, Los Angeles, California, USA.
authors.forename: Ciaren
authors.initials: C
authors.lastname: Graham
authors.forename: Hittu
authors.initials: H
authors.lastname: Matta
authors.forename: Yanqiang
authors.initials: Y
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Yi
authors.forename: Yulan
authors.initials: Y
authors.lastname: Suo
authors.forename: Bhairavi
authors.initials: B
authors.lastname: Tolani
authors.forename: Preet M
authors.initials: PM
authors.lastname: Chaudhary
mesh_terms: D000818:Animals; D017209:Apoptosis; D001402:B-Lymphocytes / Q000276:immunology* / Q000821:virology*; D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D054884:Host-Pathogen Interactions; D051379:Mice; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051841:Transcription Factor RelB / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
chemical_list: C579094:Mcl1 protein, mouse; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; C497594:Relb protein, mouse; D014764:Viral Proteins; C481275:viral FLIP protein, Human herpesvirus 8; D051841:Transcription Factor RelB