Myc is required for the maintenance of Kaposi's sarcoma-associated herpesvirus latency.
Myc is deregulated by Kaposi's sarcoma-associated herpesvirus (KSHV) latent proteins, but its role in KSHV latency is not clear. We found that Myc knockdown with RNA interference (RNAi) induced KSHV reactivation and increased the protein and mRNA levels of RTA, a key viral regulator of KSHV reactivation. Myc knockdown increased, whereas Myc overexpression inhibited, RTA promoter activity. KSHV reactivation and the activation of the RTA promoter induced by Myc depletion were inhibited by c-Jun N-terminal kinase (JNK) and p38 inhibitors but not by a MEK1 inhibitor. Myc knockdown inhibited primary effusion lymphoma (PEL) cell proliferation through inducing apoptosis and G(1) cell cycle arrest. Thus, Myc may be a key cellular node coupling cellular transformation and KSHV latency.
Li
Xudong
X
Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA.
Chen
Shijia
S
Feng
Jun
J
Deng
Hongyu
H
Sun
Ren
R
D002453:Cell Cycle; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006566:Herpesviridae Infections / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000821:virology; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000502:physiology*; D006801:Humans; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D014775:Virus Activation; D017735:Virus Latency
D016271:Proto-Oncogene Proteins c-myc