Muromoto Ryuta, Okabe Kanako, Fujimuro Masahiro, Sugiyama Kenji, Yokosawa Hideyoshi, Seya Tsukasa, Matsuda Tadashi
Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
FEBS Lett. 2006 Jan 9;580(1):93-8. doi: 10.1016/j.febslet.2005.11.057. Epub 2005 Dec 6.
The Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded latency-associated nuclear antigen (LANA) is known to modulate viral and cellular gene expression. We show that LANA directly associates with an interleukin-6 signal transducer, signal transducer and activator of transcription 3 (STAT3) and that LANA enhances the transcriptional activity of STAT3. Coimmunoprecipitation studies documented a physical interaction between LANA and STAT3 in transiently transfected 293T cells as well as the KSHV-infected primary effusion lymphoma (PEL) cell line. Furthermore, small-interfering RNA-mediated reduction of LANA expression decreased the STAT3-dependent transcription in KSHV-positive PEL cells, whereas overexpression of LANA enhanced STAT3 activity in KSHV-negative B lymphoma cells. These data demonstrate that LANA is a transcriptional co-activator of STAT3, and may have implications for the pathogenesis of KSHV-associated diseases.
已知卡波西肉瘤相关疱疹病毒（KSHV）编码的潜伏相关核抗原（LANA）可调节病毒和细胞基因表达。我们发现，LANA直接与白细胞介素-6信号转导子、信号转导和转录激活因子3（STAT3）相关联，并且LANA可增强STAT3的转录活性。免疫共沉淀研究证明，在瞬时转染的293T细胞以及KSHV感染的原发性渗出性淋巴瘤（PEL）细胞系中，LANA与STAT3之间存在物理相互作用。此外，小干扰RNA介导的LANA表达降低减少了KSHV阳性PEL细胞中STAT3依赖性转录，而LANA的过表达增强了KSHV阴性B淋巴瘤细胞中的STAT3活性。这些数据表明，LANA是STAT3的转录共激活因子，可能与KSHV相关疾病的发病机制有关。
