Protein Modification and Autophagy Activation

  • Rui Wang
  • Guanghui WangEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1206)


Protein modification refers to the chemical modification of proteins after their biosynthesis, which is also called posttranslational modification (PTM). PTM causes changes in protein properties and functions. PTM includes an attachment of addition of functional groups, such as methylation, acetylation, glycosylation and phosphorylation; a covalent coupling of small peptides or proteins, such as ubiquitination and SUMOylation; or chemical changes in amino acids, such as citrullination (conversion of arginine to citrulline). Protein modification plays an important role in cellular processes. Since a protein can be modified in different ways, such as acetylation, methylation and phosphorylation, the functions of proteins are different under different modification states. Moreover, the same modification at different sites may have completely different effects on protein function. For example, phosphorylation at some sites in a protein may lead to a functional activation, while phosphorylation at other sites may cause an inhibition of the functions. Thus, different modifications, combinations and sites changes lead to different functional regulations of a protein, resulting in different effects in the cells. In autophagy, PTMs are widely involved in the regulation of autophagy, including ubiquitination, phosphorylation and acetylation. Ubiquitination is the covalent conjugation of ubiquitin to the substrates through a series of enzymes. Phosphorylation refers to an attachment of a phosphoryl group into a protein, primarily on serine, threonine and tyrosine, which is catalyzed by the kinases. Phosphorylation, a common modification, regulates protein function and localization. Phosphorylation in autophagy regulates the activity of autophagy-associated proteins and the initiation and progression of autophagy by regulating signaling pathways. Acetylation means the addition of acetyl groups onto lysine or N-terminal segment of target proteins through acetyltransferases. Acetylation and deacetylation are both involved in the regulation of autophagy initiation and selective autophagy by controlling the acetylation level of important proteins in the autophagy process. In this chapter, we will focus on the regulation of ubiquitination and phosphorylation in autophagy.


UPS ALS Ubiquitination Phosphorylation Acetylation Autophagy Autophagy receptors 



Autophagy-lysosome system


AMP-regulated protein kinase


Coiled-coil domain


C-terminal domain


Cytoplasm-to-vacuole target


Ubiquitin-activating enzyme


Ubiquitin-conjugating enzyme


Ubiquitin ligase


Histone deacetylase 6


LC3-interacting region


Mitogen-activated protein kinase


Neighbor of breast cancer 1




Pre-autophagosomal structure






PI3K class III complex




Protein kinase C


Protein phosphatase




Target of rapamycin complex 1


Tuberous sclerosis complex 2






Unc-51-like kinase


Ubiquitin-proteasome system


Zinc finger


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Copyright information

© Science Press and Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Laboratory of Molecular Neuropathology, Jiangsu Key Laboratory of Neuropsychiatric Diseases & Department of Pharmacology, College of Pharmaceutical SciencesSoochow UniversitySuzhouChina

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