Physiology and pathophysiology of a human endogenous retrovirus encoded protease that processes disease-relevant cellular proteins

大约8%的人类基因组质量是由数百万年前外源性逆转录病毒感染生殖系细胞的序列组成的。所谓的人类内源性逆转录病毒（herv）通常由于长期存在于基因组中而获得大量突变，不再编码以前的逆转录病毒蛋白。例外情况包括由HERV-W组编码的一种蛋白质，这种蛋白质对胎盘发育至关重要，以及由所谓的HERV-K（HML-2）组的年轻基因座编码的各种蛋白质。许多herv，包括HERV-K(HML-2)，仍然在良性条件下转录，并且在各种疾病中以不受管制的方式转录。HERV表达在多种类型的癌症和神经退行性疾病中具有功能作用。HERV-K（HML-2）编码一种功能性蛋白酶，该蛋白酶通常处理HERV-K(HML-2) Gag蛋白。我们在最近的研究中确定HERV-K（HML-2）蛋白酶也加工许多细胞蛋白，其中包括许多疾病相关蛋白。因此，HERV-K（HML-2）蛋白酶的表达失调伴随着疾病相关细胞蛋白的降解，可能有助于人类疾病的发展。在当前的研究中，我们将进一步研究HERV-K（HML-2）蛋白酶的作用，重点关注HERV-K（HML-2）蛋白酶在细胞生物学和潜在疾病相关性方面的具体方面。我们的研究将为更具体地研究HERV-K（HML-2）蛋白酶加工细胞蛋白的细胞后果提供额外的重要数据。

Approximately 8% of the human genome mass consists of sequences that derive from infections of germ line cells by exogenous retroviruses millions of years ago. So-called human endogenous retroviruses (HERVs) usually acquired numerous mutations due to long-time presence in the genome and no longer encode former retroviral proteins. Exceptions include a protein encoded by the HERV-W group that appears essential for placenta development and various proteins encoded by evolutionarily young loci of the so-called HERV-K(HML-2) group. Many HERVs, including HERV-K(HML-2), are still transcribed in benign conditions and in a deregulated fashion in various diseases. A functional role of HERV expression has been suggested recently for various types of cancer and neurodegenerative diseases. HERV-K(HML-2) encodes a functional protease that typically processes HERV-K(HML-2) Gag protein. We established in our recent research that HERV-K(HML-2) protease does also process numbers of cellular proteins, among them many disease-relevant proteins. Deregulated expression of HERV-K(HML-2) protease accompanied by degradation of disease-relevant cellular proteins therefore may contribute to development of human diseases. In the current research, we will further investigate the role of HERV-K(HML-2) protease by focusing on specific aspects of the cell biology and potential disease relevance of HERV-K(HML-2) protease. Our research will generate additional important data for more specific investigations of cellular consequences of processing of cellular proteins by HERV-K(HML-2) protease.