Mahatma Gandhi Medical Advanced Research Institute (MGMARI), Sri Balaji Vidyapeeth, Puducherry, 607 402, India.
Department of Biochemistry and Molecular Biology, Pondicherry University, Puducherry, 605 014, India.
Funct Integr Genomics. 2024 Sep 3;24(5):152. doi: 10.1007/s10142-024-01426-8.
In the complex landscape of cancer biology, the discovery of microproteins has triggered a paradigm shift, thereby, challenging the conventional conceptions of gene regulation. Though overlooked for years, these entities encoded by the small open reading frames (100-150 codons), have a significant impact on various cellular processes. As precision medicine pioneers delve deeper into the genome and proteome, microproteins have come into the limelight. Typically characterized by a single protein domain that directly binds to the target protein complex and regulates their assembly, these microproteins have been shown to play a key role in fundamental biological processes such as RNA processing, DNA repair, and metabolism regulation. Techniques for identification and characterization, such as ribosome profiling and proteogenomic approaches, have unraveled unique mechanisms by which these microproteins regulate cell signaling or pathological processes in most diseases including cancer. However, the functional relevance of these microproteins in cancer remains unclear. In this context, the current review aims to "rethink the essence of these genes" and explore "how these hidden players-microproteins orchestrate the signaling cascades of cancer, both as accelerators and brakes.".
在癌症生物学的复杂领域中,微小蛋白的发现引发了范式转变,从而挑战了传统的基因调控观念。尽管这些微小蛋白被小开放阅读框(100-150 个密码子)编码,多年来一直被忽视,但它们对各种细胞过程有着重大影响。随着精准医学的先驱者深入研究基因组和蛋白质组,微小蛋白开始受到关注。这些微小蛋白通常具有一个单一的蛋白质结构域,直接与靶蛋白复合物结合并调节其组装,它们被证明在 RNA 处理、DNA 修复和代谢调节等基本生物过程中发挥关键作用。鉴定和表征技术,如核糖体图谱分析和蛋白质基因组学方法,揭示了这些微小蛋白调节细胞信号或包括癌症在内的大多数疾病中病理过程的独特机制。然而,这些微小蛋白在癌症中的功能相关性尚不清楚。在这种情况下,目前的综述旨在“重新思考这些基因的本质”,并探讨“这些隐藏的参与者——微小蛋白如何作为加速器和制动器来协调癌症的信号级联。”