NDLI: A20 Is Induced by Kaposi Sarcoma-associated Herpesvirus-encoded Viral FLICE Inhibitory Protein (vFLIP) K13 and Blocks K13-induced Nuclear Factor-κB in a Negative Feedback Manner*

Content Provider	PubMed Central
Author	Matta, Hittu Gopalakrishnan, Ramakrishnan Punj, Vasu Yi, Han Suo, Yulan Chaudhary, Preet M.
Copyright Year	2011
Abstract	Expression of A20, a negative regulator of the NF-κB pathway, is frequently lost in several subtypes of Hodgkin and non-Hodgkin lymphoma. We report that A20 is expressed in Kaposi sarcoma-associated herpesvirus (KSHV)-infected primary effusion lymphoma cell lines, and its expression correlates closely with the expression of KSHV-encoded viral FLICE inhibitory protein K13. Ectopic expression of K13 induced A20 expression through NF-κB-mediated activation of A20 promoter. In turn, A20 blocked K13-induced NF-κB activity and up-regulation of proinflammatory cytokines CCL20 and IL-8 in a negative feedback fashion. Both the N-terminal deubiquitinating domain and the C-terminal zinc finger domain of A20 were involved in the inhibition of K13-induced NF-κB activity. Overexpression of A20 blocked K13-induced IκBα phosphorylation, NF-κB nuclear translocation, and cellular transformation. Consistent with the above, K13-induced IκBα phosphorylation and NF-κB transcriptional activation were enhanced in A20-deficient cells. Finally, A20 was found to interact physically with K13. Taken collectively, these results demonstrate that K13 is a key determinant of A20 expression in KSHV-infected cells, and A20 is a key negative regulator of K13-induced NF-κB activity. A20 might serve to control the inflammatory response to KSHV infection and protect KSHV-infected cells from apoptosis.
Related Links	http://dx.doi.org/10.1074/jbc.m111.224048
Ending Page	21564
Page Count	10
Starting Page	21555
File Format	PDF
ISSN	00219258
e-ISSN	1083351X
Journal	The Journal of Biological Chemistry
Issue Number	24
Volume Number	286
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2011-06-17
Access Restriction	Open
Rights Holder	American Society for Biochemistry and Molecular Biology
Subject Keyword	Cell Biology Biochemistry Molecular Biology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cell Biology Biochemistry Molecular Biology

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