Department of Microbiology, Anhui Medical University, Hefei 230032, China.
Department of Physiology, Anhui Medical University, Hefei 230032, China.
Viruses. 2018 May 24;10(6):282. doi: 10.3390/v10060282.
Kaposi's sarcoma (KS) is a tumor of the vascular endothelium that is caused by Kaposi's sarcoma-associated herpesvirus (KSHV). K15 of KSHV is a specific gene encoding a transmembrane protein. Two highly different forms of K15, the predominant (K15P) and minor (K15M) have been identified in different KSHV strains. In genomic locations and protein topology, two K15 alleles resemble the latent membrane protein (LMP) 1 and LMP2A of Epstein⁻Barr virus. Both K15 proteins have motifs similar to those found in LMP1 and LMP2A. K15 therefore seems to be a hybrid of a distant evolutionary relative of LMP1 and LMP2A. Ca is a second messenger and participates in numerous activities in cells, like proliferation, migration and metastasis. It has been found previously that LMP1 increased Ca influx through store-operated calcium channels and blockade of LMP1 reduced store-operated Ca entry (SOCE). LMP2A has similar activity. So we sought to determine whether K15 had similar activity. We showed that K15P induced Ca influx and enhanced expression of Orail1, which is a vital protein in SOCE, and overexpression of K15P improved cell motility. Mutant K15P did not show these activities in HEK-293T and EA.hy 926 cells. Our results showed that K15P increased cell proliferation and migration though SOCE and established a novel mechanism for the development of KS and KSHV-associated diseases.
卡波西肉瘤（KS）是一种血管内皮细胞肿瘤，由卡波西肉瘤相关疱疹病毒（KSHV）引起。KSHV 的 K15 是一种编码跨膜蛋白的特异性基因。在不同的 KSHV 株中已经鉴定出两种高度不同的 K15 形式，主要（K15P）和次要（K15M）。在基因组位置和蛋白质拓扑结构上，两个 K15 等位基因类似于 EBV 的潜伏膜蛋白（LMP）1 和 LMP2A。两种 K15 蛋白都具有与 LMP1 和 LMP2A 相似的基序。因此，K15 似乎是 LMP1 和 LMP2A 的远缘进化相关蛋白的杂交体。Ca 是第二信使，参与细胞中的许多活动，如增殖、迁移和转移。先前已经发现，LMP1 通过储存操纵钙通道增加 Ca 内流，并且 LMP1 的阻断减少了储存操纵的 Ca 进入（SOCE）。LMP2A 具有类似的活性。因此，我们试图确定 K15 是否具有类似的活性。我们表明，K15P 诱导 Ca 内流并增强了 SOCE 中至关重要的蛋白 Orail1 的表达，并且 K15P 的过表达改善了细胞迁移性。突变型 K15P 在 HEK-293T 和 EA.hy 926 细胞中没有显示出这些活性。我们的结果表明，K15P 通过 SOCE 增加细胞增殖和迁移，并建立了 KS 和 KSHV 相关疾病发展的新机制。
