Rossi Fabiana Alejandra, Rossi Mario
Genómica Funcional y Ciencia de Datos, Instituto de Investigaciones en Medicina Traslacional (IIMT), CONICET-Universidad Austral, Buenos Aires, Argentina.
Front Cell Dev Biol. 2022 May 12;10:889166. doi: 10.3389/fcell.2022.889166. eCollection 2022.
Ubiquitination and ubiquitin-like post-translational modifications control the activity and stability of different tumor suppressors and oncoproteins. Hence, regulation of this enzymatic cascade offers an appealing scenario for novel antineoplastic targets discovery. Among the different families of enzymes that participate in the conjugation of Ubiquitin, deubiquitinating enzymes (DUBs), responsible for removing ubiquitin or ubiquitin-like peptides from substrate proteins, have attracted increasing attention. In this regard, increasing evidence is accumulating suggesting that the modulation of the catalytic activity of DUBs represents an attractive point of therapeutic intervention in cancer treatment. In particular, different lines of research indicate that USP19, a member of the DUBs, plays a role in the control of tumorigenesis and cancer dissemination. This review aims at summarizing the current knowledge of USP19 wide association with the control of several cellular processes in different neoplasms, which highlights the emerging role of USP19 as a previously unrecognized prognosis factor that possesses both positive and negative regulation activities in tumor biology. These observations indicate that USP19 might represent a novel putative pharmacologic target in oncology and underscores the potential of identifying specific modulators to test in clinical settings.
泛素化和类泛素化翻译后修饰控制着不同肿瘤抑制因子和癌蛋白的活性与稳定性。因此,调控这一酶促级联反应为发现新型抗肿瘤靶点提供了一个有吸引力的方向。在参与泛素缀合的不同酶家族中,负责从底物蛋白上移除泛素或类泛素肽段的去泛素化酶(DUBs)已引起越来越多的关注。在这方面,越来越多的证据表明,调节DUBs的催化活性是癌症治疗中一个有吸引力的治疗干预点。特别是,不同的研究方向表明,DUBs家族成员之一的USP19在肿瘤发生和癌症扩散的控制中发挥作用。本综述旨在总结目前关于USP19与不同肿瘤中多种细胞过程控制广泛关联的知识,这凸显了USP19作为一个先前未被认识的预后因子在肿瘤生物学中具有正负调控活性的新作用。这些观察结果表明,USP19可能是肿瘤学中一个新的潜在药理学靶点,并强调了识别特定调节剂用于临床测试的潜力。