Sreedhar Annapoorna, Wiese Elizabeth K, Hitosugi Taro
Department of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
Division of Oncology Research, Mayo Clinic, Rochester, MN, USA.
Genes Dis. 2019 Oct 8;7(2):166-171. doi: 10.1016/j.gendis.2019.09.011. eCollection 2020 Jun.
Lysine succinylation (Ksucc), defined as a transfer of a succinyl group to a lysine residue of a protein, is a newly identified protein post-translational modification. This chemical modification is reversible, dynamic, and evolutionarily conserved where it has been comprehensively studied in both bacterial and mammalian cells. Numerous proteins involved in the regulation of various cellular and biological processes have been shown to be heavily succinylated. Emerging clinical data provides evidence that dysregulation of Ksucc is correlated with the development of several diseases, including cardiovascular diseases and cancer. Therefore, an in-depth understanding of Ksucc and its regulation is important not only for understanding its physiological function but also for developing drug therapies and targeted agents for these diseases. In this review, we highlight some of the recent advances in understanding the role of Ksucc and desuccinylation under physiological and pathological conditions.
赖氨酸琥珀酰化(Ksucc)是指琥珀酰基团转移到蛋白质的赖氨酸残基上,是一种新发现的蛋白质翻译后修饰。这种化学修饰是可逆的、动态的,并且在进化上是保守的,已经在细菌和哺乳动物细胞中进行了全面研究。许多参与各种细胞和生物过程调控的蛋白质已被证明高度琥珀酰化。新出现的临床数据表明,Ksucc失调与包括心血管疾病和癌症在内的几种疾病的发生有关。因此,深入了解Ksucc及其调控不仅对于理解其生理功能很重要,而且对于开发这些疾病的药物疗法和靶向药物也很重要。在这篇综述中,我们重点介绍了在理解生理和病理条件下Ksucc和去琥珀酰化作用方面的一些最新进展。