Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-κB activation

Ciaren Graham, Hittu Matta, Yanqiang Yang, Han Yi, Yulan Suo, Bhairavi Tolani, Preet M. Chaudhary*

*Corresponding author for this work

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 p27Kip1 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.

Original languageEnglish
Pages (from-to)2242-2252
Number of pages11
JournalJournal of Virology
Volume87
Issue number4
DOIs
Publication statusPublished - 01 Feb 2013

Fingerprint

Human herpesvirus 8
Human Herpesvirus 8
Oncogene Proteins
B-lymphocytes
B-Lymphocytes
apoptosis
Apoptosis
receptors
CASP8 and FADD-Like Apoptosis Regulating Protein
Growth
Viral Proteins
Primary Effusion Lymphoma
cell lines
Cell Line
lymphatic diseases
B-Lymphoid Precursor Cells
Lymphoproliferative Disorders
Kaposi's Sarcoma
sarcoma
lymphoma

Cite this

Graham, Ciaren ; Matta, Hittu ; Yang, Yanqiang ; Yi, Han ; Suo, Yulan ; Tolani, Bhairavi ; Chaudhary, Preet M. / Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-κB activation. In: Journal of Virology. 2013 ; Vol. 87, No. 4. pp. 2242-2252.
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Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-κB activation. / Graham, Ciaren; Matta, Hittu; Yang, Yanqiang; Yi, Han; Suo, Yulan; Tolani, Bhairavi; Chaudhary, Preet M.

In: Journal of Virology, Vol. 87, No. 4, 01.02.2013, p. 2242-2252.

Research output: Contribution to journalArticle

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T1 - Kaposi's sarcoma-associated herpesvirus oncoprotein K13 protects against B cell receptor-induced growth arrest and apoptosis through NF-κB activation

AU - Graham, Ciaren

AU - Matta, Hittu

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AU - Yi, Han

AU - Suo, Yulan

AU - Tolani, Bhairavi

AU - Chaudhary, Preet M.

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AB - 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 p27Kip1 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.

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