Abstract:
Programmed ribosomal frameshifting (PRF) is a key mechanism that viruses use to generate essential proteins for replication, and as a means of regulating gene expression. PRF generally involves recoding signals or frameshift stimulators to elevate the occurrence of frameshifting at shift-prone \'slippery\' sequences. Given its essential role in viral replication, targeting PRF was envisioned as an attractive tool to block viral infection. However, in contrast to controlled-PRF mechanisms, recent studies have shown that ribosomes of many human cancer cell types are prone to frameshifting upon amino acid shortage; thus, these cells are deemed to be sloppy. The resulting products of a sloppy frameshift at the \'hungry\' codons are aberrant proteins the degradation and display of which at the cell surface can trigger T cell activation. In this review, we address recent discoveries in ribosomal frameshifting and their functional consequences for the proteome in human cancer cells.
摘要:
程序化核糖体移码(PRF)是病毒用来产生复制必需蛋白的关键机制,作为调节基因表达的手段。PRF通常涉及重新编码信号或移码刺激器,以提高易变序列中移码的发生。鉴于其在病毒复制中的重要作用,靶向PRF被认为是阻断病毒感染的有吸引力的工具.然而,与受控PRF机制相反,最近的研究表明,许多人类癌细胞类型的核糖体在氨基酸短缺时容易发生移码;因此,这些细胞被认为是草率的。在“饥饿”密码子处草率移码的产物是异常蛋白质,其降解和在细胞表面的显示可以触发T细胞活化。在这次审查中,我们讨论了核糖体移码的最新发现及其对人类癌细胞蛋白质组的功能影响。