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