Universität zu Köln

Liebl, Martina P. and Hoppe, Thorsten ORCID: 0000-0002-4734-9352 (2016). It's all about talking: two-way communication between proteasomal and lysosomal degradation pathways via ubiquitin. Am. J. Physiol.-Cell Physiol., 311 (2). S. C166 - 13. BETHESDA: AMER PHYSIOLOGICAL SOC. ISSN 1522-1563

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Abstract

Selective degradation of proteins requires a fine-tuned coordination of the two major proteolytic pathways, the ubiquitin-proteasome system (UPS) and autophagy. Substrate selection and proteolytic activity are defined by a plethora of regulatory cofactors influencing each other. Both proteolytic pathways are initiated by ubiquitylation to mark substrate proteins for degradation, although the size and/or topology of the modification are different. In this context E3 ubiquitin ligases, ensuring the covalent attachment of activated ubiquitin to the substrate, are of special importance. The regulation of E3 ligase activity, competition between different E3 ligases for binding E2 conjugation enzymes and substrates, as well as their interplay with deubiquitylating enzymes (DUBs) represent key events in the cross talk between the UPS and autophagy. The coordination between both degradation routes is further influenced by heat shock factors and ubiquitin-binding proteins (UBPs) such as p97, p62, or optineurin. Mutations in enzymes and ubiquitin-binding proteins or a general decline of both proteolytic systems during aging result in accumulation of damaged and aggregated proteins. Thus further mechanistic understanding of how UPS and autophagy communicate might allow therapeutic intervention especially against age-related diseases.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Liebl, Martina P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hoppe, Thorsten UNSPECIFIED orcid.org/0000-0002-4734-9352 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-267415
DOI:	10.1152/ajpcell.00074.2016
Journal or Publication Title:	Am. J. Physiol.-Cell Physiol.
Volume:	311
Number:	2
Page Range:	S. C166 - 13
Date:	2016
Publisher:	AMER PHYSIOLOGICAL SOC
Place of Publication:	BETHESDA
ISSN:	1522-1563
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language AMYOTROPHIC-LATERAL-SCLEROSIS; VALOSIN-CONTAINING PROTEIN; LIFE-SPAN EXTENSION; ENDOPLASMIC-RETICULUM STRESS; SKELETAL-MUSCLE ATROPHY; GENE-EXPRESSION PROFILE; CAENORHABDITIS-ELEGANS; QUALITY-CONTROL; C-ELEGANS; CELL-DEATH Multiple languages Cell Biology; Physiology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26741