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Dancing while self-eating: Protein intrinsic disorder in autophagy.

Author
Abstract
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Autophagy is a major catabolic pathway that must be tightly regulated to maintain cellular homeostasis. Protein intrinsic disorder provides a very suitable conformation for regulation; accordingly, the molecular machinery of autophagy is significantly enriched in intrinsically disordered proteins and protein regions (IDPs/IDPRs). Despite experimental challenges that the characterization of IDPRs encounters, remarkable progress has been made in recent years in revealing various roles of IDPs/IDPRs in autophagy. This chapter describes the autophagy pathway from a specific point of view, that of IDPRs. It focuses in detail on structural and mechanistic functions in autophagy that are executed by disordered regions. Via a description of autophagosome biogenesis, linking the cargo to the autophagy machinery, as well as a discussion of certain post-translational regulations, this review reveals many indispensable roles of IDPRs in the functional autophagy pathway. Devastating pathologies such as neurodegeneration, cancer, or diabetes have been linked to a malfunction in IDPs/IDPRs. The same pathologies are associated with dysfunctional autophagy, indicating that autophagic IDPRs may be a paramount causative factor. Several disease-related mechanisms of the autophagy pathway involving protein intrinsic disorder are reported in this chapter, to illustrate a wide-ranging potential of IDPRs in the therapeutic modulation of autophagy.

Year of Publication
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0
Journal
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Progress in molecular biology and translational science
Volume
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174
Number of Pages
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263-305
Date Published
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2020
ISSN Number
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1877-1173
URL
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https://linkinghub.elsevier.com/retrieve/pii/S1877-1173(20)30037-5
DOI
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10.1016/bs.pmbts.2020.03.002
Short Title
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Prog Mol Biol Transl Sci
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