The Kaposin B protein of KSHV Activates the p38/MK2 Pathway and Stabilizes Cytokine mRNAs

Science 2005 307:739-41

Speaker: 姚蕙雯

Commentator: 楊倍昌  教授

Time: 2005.03.30 14:00-15:00

Abstract:

Kaposi’s sarcoma-associated herpesvirus (KSHV), the etiological agent of Kaposi’s sarcoma and several lymphoproliferative diseases, is first identified as herpesvirus-like DNA sequences in AIDS-associated Kaposi’s sarcoma at 1994¹.  An important characteristic of KSHV-induced diseases is the high level of cytokine production².  However, the mechanism that contributes to the elevated cytokine production has not been identified.  In this study, kaposin B protein, a product of the kaposin locus during latency, is found to interact with MAPK-associated protein kinase 2 (MK2), which contributes to the stabilization of mRNAs containing AU-rich elements (AREs)³, especially cytokine transcripts.  While binding to kaposin B protein, MK2 is activated to abrogate ARE-mediated degradation of cytokine transcripts and subsequently promotes cytokine production.  Although the actual mechanism that kaposin B protein expression leads to activation of MK2 is incomplete, it is proposed that binding of MK2 by kaposin B protein directly promotes MK2 activation, and the enhanced activity of p38 amplifies the initial effect.  In addition, the augmentation of cytokine production in kaposin B-expressing cells might further stimulate p38/MK2 pathway through autocrine or paracrine loop.  This study provides an explanation for elevated cytokine production in KSHV-associated diseases irrespective of the mechanistic details.

References:

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