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卡波氏肉瘤相关疱疹病毒(KSHV)编码的G-蛋白偶联受体(vGPCR)是一种致瘤蛋白,它与KSHV相关恶性肿瘤的发生密切相关.本工作组前期研究发现,vGPCR胞外氨基端(N端)第26位和第28位酪氨酸(Y26和Y28)均具有巯基化修饰,且该巯基化修饰对于vGPCR在裸鼠中的致瘤性至关重要.hGRO-可结合巯基化的vGPCR,并通过自分泌促进其致瘤性.有趣的是,未巯基化的vGPCR突变体(yydd-vGPCR)削弱由hGRO-导致的肿瘤的发生.本研究表达和纯化了vGPCR的N端(wt-vGN)和未巯基化的vGPCR突变体的N端(yydd-vGN).放射性标记实验结果表明,wt-vGN而非yydd-vGN可结合[35S]标记的硫酸盐.在裸鼠实验中,稳定表达yydd-vGN的NIH3T3细胞而非稳定表达wt-vGN的NIH3T3细胞可强烈抑制hGRO-导致的肿瘤发生.本研究证明,未巯基化的vGPCR胞外N端的可降低hGRO-在裸鼠中的致瘤性.
Kaposi’s sarcoma-associated herpesvirus (KSHV) encodes a G-protein coupled receptor (vGPCR) is a tumorigenic protein that is closely related to the occurrence of KSHV-related malignancies.Previous studies in this group found that vGPCR extracellular Both tyrosine (Y26 and Y28) at amino-terminal (N-terminal) and tyrosine at position 28 (Y26 and Y28) have thiolated modifications, and this thiolation modification is crucial for the oncogenicity of vGPCR in nude mice. Thiolated vGPCR and promoted its tumorigenicity through autocrine.It is interesting that the un-thiolated vGPCR mutant (yydd-vGPCR) impaired the hGRO-induced tumorigenesis.In this study, the expression and purification of vGPCR in N (Wt-vGN) and non-thiolated vGPCR mutants.The results of radiolabeling indicated that wt-vGN, but not yydd-vGN, could bind to [35S] -labeled sulfate.In nude mice In experiments, NIH3T3 cells stably expressing yydd-vGN, but not NIH3T3 cells stably expressing wt-vGN, strongly inhibited hGRO-induced tumorigenesis.This study demonstrated that extracellular N-terminal of vTLD without thiolation reduced hGRO- Tumorigenicity in rats.