Abstract

The serine/threonine kinase mammalian target of rapamycin (mTOR) is the catalytic subunit of two complexes, mTORC1 and mTORC2, which have common and distinct subunits that mediate separate and overlapping functions. mTORC1 is activated by plenty of nutrients, and the two complexes can be activated by PI3K signaling. mTORC2 acts as an upstream regulator of AKT, and mTORC1 acts as a downstream effector. mTOR signaling integrates both intracellular and extracellular signals, acting as a key regulator of cellular metabolism, growth, and survival. A dysregulated activation of mTOR, as result of PI3K pathway or mTOR regulatory protein mutations or even due to the presence of cellular or viral oncogenes, is a common finding in cancer and represents a central mechanism in cancerogenesis. In the final part of this review, we will focus on the PI3K/AKT/mTOR activation by the human gammaherpesviruses EBV and KSHV that hijack this pathway to promote their-mediated oncogenic transformation and pathologies.

摘要

雷帕霉素的丝氨酸/苏氨酸激酶哺乳动物靶标 (mTOR) 是两个复合物 mTORC1 和 mTORC2 的催化亚基，它们具有共同和不同的亚基，可介导单独和重叠的功能。mTORC1 被大量的营养物质激活，这两个复合物可以被 PI3K 信号激活。mTORC2 充当 AKT 的上游调节剂，mTORC1 充当下游效应器。mTOR 信号整合了细胞内和细胞外信号，作为细胞代谢、生长和存活的关键调节剂。由于 PI3K 通路或 mTOR 调节蛋白突变，甚至由于细胞或病毒癌基因的存在，mTOR 的异常激活是癌症中的常见发现，并且代表了癌症发生的中心机制。在这篇评论的最后部分，