KAPOSIS SARCOMA ASSOCIATED HERPESVIRUS ENCODES FUNCTIONAL CYCLIN

卡波西肉瘤相关疱疹病毒含有一种编码 细胞周期蛋白(v-Cyclin)。KSHV v-Cyclin确实是一种调节因子 细胞周期蛋白依赖性激酶的亚基6.卡波西氏 肉瘤相关疱疹病毒(又称人类疱疹病毒) 8)在Kaposi肉瘤病变和 体腔为基础的淋巴瘤。获得了一个17kb的KSHV lambda克隆 直接来自卡波西肉瘤的病变。日本血吸虫DNA序列分析 该克隆鉴定出一个含有32%氨基酸的开放呈现框。 与病毒编码的细胞周期蛋白(v-Cyclin)的同源性和53%的相似性 与人类疱疹病毒31%的同源性和53%的相似性 细胞周期蛋白D2。该KSHV开放阅读框被显示为编码 一种29到30 kDa的蛋白质，具有v-细胞周期蛋白的特性。KSHV V-Cyclin蛋白主要与CDK6、 已知与细胞型相互作用的细胞周期蛋白依赖性激酶 D-细胞周期蛋白和HVS-V-细胞周期蛋白。KSHV v-Cyclin也被发现 CDK4与CDK4结合较弱。KSHV v-细胞周期蛋白-CDK6强络合物 磷酸化谷胱甘肽S-转移酶-Rb融合蛋白与组蛋白 H1作为体外培养的底物。因此，KSHV的v-细胞周期蛋白类似于v-细胞周期蛋白 T淋巴细胞转化人免疫缺陷病毒的特异性 与CDK6的相关性及其强烈激活CDK6的能力 蛋白激酶活性。

Kaposi's sarcoma-associated herpesvirus contains a virus-encoded cyclin (v-cyclin). KSHV v-cyclin indeed functions as a regulatory subunit of a cellular cyclin-dependent kinase 6. Kaposi's sarcoma-associated herpesvirus (KSHV) (also called human herpesvirus 8) is consistently found in Kaposi's sarcoma lesions and in body-cavity-based lymphomas. A 17-kb KSHV lambda clone was obtained directly from a Kaposi's sarcoma lesion. DNA sequence analysis of this clone identified an open rending frame which has 32% amino acid identity and 53% similarity to the virus-encoded cyclin (v-cyclin) of herpesvirus saimiri (HVS) and 31% identity and 53% similarity to human cellular cyclin D2. This KSHV open reading frame was shown to encode a 29- to 30-kDa protein with the properties of a v-cyclin. KSHV v-cyclin protein was found to associate predominantly with cdk6, a cellular cyclin-dependent kinase known to interact with cellular type D cyclins and HVS v-cyclin. The KSHV v-cyclin was also found to associate weakly with cdk4. KSHV v-cyclin-cdk6 complexes strongly phosphorylated glutathione S-transferase-Rb fusion protein and histone H1 as substrates in vitro. Thus, KSHV v-cyclin resembles the v-cyclin of the T-lymphocyte-transforming HVS in its specificity for association with cdk6 and in its ability to strongly activate cdk6 protein kinase activity.