卡波氏肉瘤（KS）是一种血管内皮来源的恶性肿瘤，常见于艾滋病患者。卡波氏肉瘤相关疱疹病毒（KSHV）是导致KS的直接病因。KSHV潜伏态相关核抗原LANA在KS发生的过程中起关键作用。我们通过串联亲和纯化-质谱（TAP-MS）的方法发现SMAD1是LANA潜在的相互作用蛋白。研究表明SMAD1下游重要促肿瘤生成、促血管生成因子ID1在KS高表达，而ID１在KS中上调的机制和功能尚未阐明。我们推测LANA通过与SMAD1相互作用，稳定磷酸化SMAD1在核内的表达，促进SMAD1对ID1的转录激活作用，从而上调ID1表达并促进KS的发生和发展。本研究中，我们将通过证明LANA是否通过结合SMAD1并上调ID1表达以及LANA是否通过上调ID1表达促进KSHV感染细胞的血管生成、增殖以及转化。从机制和功能两方面来证实我们的假说。本项目对于深入理解KSHV致瘤机制以及设计KS靶向治疗具有重要意义。

Kaposi's Sarcoma (KS) is a kind of malignancy that arises from vascular endothelial and always attacks AIDS patients. Kaposi's Sarcoma associated herpesvirus (KSHV) is the etiological agent of KS.KSHV latency associated nuclear antigen (LANA) plays a key role in the processing of KS. We have identified SMAD1 as a potential LANA-binding protein through tandem affinity purification-mass spectrum method (TAP-MS).It is reported that ID1, a important pro-oncogenic and pro-angiogenic gene downstreamed of SMAD1 is overexpressed in KS,yet the mechanism and function of ID1 upregulation in KS is not clear.Therefore, we speculate that LANA stablizes p-SMAD1 expression in neucleus through binding with SMAD1 and thereby enhances SMAD1-mediated transtription activation of ID1,which will then promote the onset and processing of KS. To testify our hypothesis from mechanism to function, we will prove whether LANA up-regulates ID1 expression through binding with SMAD1 and we will prove whether LANA promotes angiogenesis, proliferation and transformation of KSHV-infected cell via up-regulation of ID1. This project is of unique significance in understanding the insight of KSHV oncogenesis and designing targeted therapy for KS.