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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsAbbreviations
- 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
References
Barutcu SA, Girnius N, Vernia S et al (2018) Role of the MAPK/cJun NH2-terminal kinase signaling pathway in starvation-induced autophagy. Autophagy 14:1586–1595
Calderilla-Barbosa L, Seibenhener ML, Du Y et al (2014) Interaction of SQSTM1 with the motor protein dynein–SQSTM1 is required for normal dynein function and trafficking. J Cell Sci 127:4052–4063
Farre JC, Subramani S (2016) Mechanistic insights into selective autophagy pathways: lessons from yeast. Nat Rev Mol Cell Biol 17:537–552
Gatica D, Lahiri V, Klionsky DJ (2018) Cargo recognition and degradation by selective autophagy. Nat Cell Biol 20:233–242
Hurley JH, Young LN (2017) Mechanisms of autophagy initiation. Annu Rev Biochem 86:225–244
Kaufmann A, Beier V, Franquelim HG et al (2014) Molecular mechanism of autophagic membrane-scaffold assembly and disassembly. Cell 156:469–481
Kirkin V, Lamark T, Sou YS et al (2009) A role for NBR1 in autophagosomal degradation of ubiquitinated substrates. Mol Cell 33:505–516
Kwon YT, Ciechanover A (2017) The ubiquitin code in the ubiquitin-proteasome system and autophagy. Trends Biochem Sci 42:873–886
Lee Y, Weihl CC (2017) Regulation of SQSTM1/p62 via UBA domain ubiquitination and its role in disease. Autophagy 13:1615–1616
Lu K, Psakhye I, Jentsch S (2014) A new class of ubiquitin-Atg8 receptors involved in selective autophagy and polyQ protein clearance. Autophagy 10:2381–2382
Menon MB, Dhamija S (2018) Beclin 1 phosphorylation—at the center of autophagy regulation. Front Cell Dev Biol 6:137
Munson MJ, Ganley IG (2015) MTOR, PIK3C3, and autophagy: signaling the beginning from the end. Autophagy 11:2375–2376
Nazio F, Cecconi F (2017) Autophagy up and down by outsmarting the incredible ULK. Autophagy 13:967–968
Peng H, Yang J, Li G et al (2017) Ubiquitylation of p62/sequestosome1 activates its autophagy receptor function and controls selective autophagy upon ubiquitin stress. Cell Res 27:657–674
Pyo KE, Kim CR, Lee M et al (2018) ULK1 O-GlcNAcylation is crucial for activating VPS34 via ATG14L during autophagy initiation. Cell Rep 25(2878–2890):e2874
Rape M (2018) Ubiquitylation at the crossroads of development and disease. Nat Rev Mol Cell Biol 19:59–70
Russell RC, Yuan HX, Guan KL (2014) Autophagy regulation by nutrient signaling. Cell Res 24:42–57
Saxton RA, Sabatini DM (2017) mTOR signaling in growth, metabolism, and disease. Cell 168:960–976
Stjepanovic G, Baskaran S, Lin MG et al (2017) Vps34 kinase domain dynamics regulate the autophagic PI 3-kinase complex. Mol Cell 67(528–534):e523
Xia Q, Wang H, Hao Z et al (2016) TDP-43 loss of function increases TFEB activity and blocks autophagosome-lysosome fusion. EMBO J 35:121–142
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2019 Science Press and Springer Nature Singapore Pte Ltd.
About this chapter
Cite this chapter
Wang, R., Wang, G. (2019). Protein Modification and Autophagy Activation. In: Qin, ZH. (eds) Autophagy: Biology and Diseases. Advances in Experimental Medicine and Biology, vol 1206. Springer, Singapore. https://doi.org/10.1007/978-981-15-0602-4_12
Download citation
DOI: https://doi.org/10.1007/978-981-15-0602-4_12
Published:
Publisher Name: Springer, Singapore
Print ISBN: 978-981-15-0601-7
Online ISBN: 978-981-15-0602-4
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)