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Leuk Lymphoma. 2015 Jan;56(1):194-201. doi: 10.3109/10428194.2014.911860. Epub 2014 Jun 25.

PKD1 is critical for Epstein-Barr virus LMP1-induced protection of malignant B cells from cell death induced by rituximab.

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  • 1Biomedical Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine , Seoul , Korea.

Abstract

Protein kinase D1 (PKD1 or PKCμ) is a serine/threonine kinase that contributes to malignant progression. Although B and T cells express multiple PKCs, modulation of PKC in association with EBV has not been evaluated. In this study we examined the effects of PKD1 as a cellular target of EBV latent membrane protein-1 (LMP1) on the response of malignant B cells to rituximab and doxorubicin. LMP1 up-regulated PKD1 in malignant B cells but not in T cells. Interestingly, LMP1 stabilized PKD1 protein through direct interaction, which contributed to the survival of malignant B cells. In the absence of PKD1, LMP1 was unable to up-regulate Mcl-1. Also, PH domain and activation loop of PKD1 was critical for LMP1-mediated cell survival. PKD1 knockdown was found to be an efficient strategy to overcome resistance caused by LMP1 expression. Therefore, PKD1 could be a molecular target for therapeutic intervention in EBV-associated B cell lymphoma treatment.

KEYWORDS:

B cell lymphoma; EBV; LMP1; PKD1/PKCμ; doxorubicin; rituximab

PMID:
24707946
[PubMed - in process]
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