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Protein Modification and Autophagy Activation

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

Abstract

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.

Keywords

UPS ALS Ubiquitination Phosphorylation Acetylation Autophagy Autophagy receptors 

Abbreviation

ALS

Autophagy-lysosome system

AMPK

AMP-regulated protein kinase

CC

Coiled-coil domain

CTD

C-terminal domain

Cvt

Cytoplasm-to-vacuole target

E1

Ubiquitin-activating enzyme

E2

Ubiquitin-conjugating enzyme

E3

Ubiquitin ligase

HDAC6

Histone deacetylase 6

LIR

LC3-interacting region

MAPK

Mitogen-activated protein kinase

NBR1

Neighbor of breast cancer 1

OPTN

Optineurin

PAS

Pre-autophagosomal structure

PE

Phosphatidylethanolamine

PI

PtdIns

PI3KC3

PI3K class III complex

PI3P

PtdIns3P

PKC

Protein kinase C

PP

Protein phosphatase

PS

Proline/serine-rich

TORC1

Target of rapamycin complex 1

TSC2

Tuberous sclerosis complex 2

Ub

Ubiquitin

UBA

Ubiquitin-associated

ULK

Unc-51-like kinase

UPS

Ubiquitin-proteasome system

ZZ

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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