Department of Pharmacology and Cancer Biology, Duke University, Durham, NC 27710, U.S.A.
Essays Biochem. 2012;52:65-77. doi: 10.1042/bse0520065.
Nutrient deprivation or cellular stress leads to the activation of a catabolic pathway that is conserved across species, known as autophagy. This process is considered to be adaptive and plays an important role in a number of cellular processes, including metabolism, immunity and development. Autophagy has also been linked to diseases, such as cancer and neurodegeneration, highlighting the importance of a better insight into its regulation. In the present chapter, we discuss how PTMs (post-translational modifications) of lysine residues by acetylation and ubiquitination alter the function of key proteins involved in the activation, maturation and substrate selectivity of autophagy. We also discuss the clinical potential of targeting these modifications to modulate autophagic activities.
营养缺乏或细胞应激会导致一种在物种间保守的分解代谢途径的激活,这种途径被称为自噬。这个过程被认为是适应性的,在许多细胞过程中发挥着重要作用,包括代谢、免疫和发育。自噬也与癌症和神经退行性疾病等疾病有关,这凸显了更好地了解其调控的重要性。在本章中,我们讨论了赖氨酸残基的 PTM(翻译后修饰),如乙酰化和泛素化,如何改变参与自噬激活、成熟和底物选择性的关键蛋白的功能。我们还讨论了靶向这些修饰来调节自噬活性的临床潜力。