A role for ubiquitin in selective autophagy.
Ubiquitination is the hallmark of protein degradation by the 26S proteasome. However, the proteasome is limited in its capacity to degrade oligomeric and aggregated proteins. Removal of harmful protein aggregates is mediated by autophagy, a mechanism by which the cell sequesters cytosolic cargo and delivers it for degradation by the lysosome. Identification of autophagy receptors, such as p62/SQSTM1 and NBR1, which simultaneously bind both ubiquitin and autophagy-specific ubiquitin-like modifiers, LC3/GABARAP, has provided a molecular link between ubiquitination and autophagy. This review explores the hypothesis that ubiquitin represents a selective degradation signal suitable for targeting various types of cargo, ranging from protein aggregates to membrane-bound organelles and microbes.
Kirkin
Vladimir
V
Institute of Biochemistry II and Cluster of Excellence Macromolecular Complexes, Goethe University, Theodor-Stern-Kai 7, Frankfurt, Germany. vladimir.chirchin@merck.de
McEwan
David G
DG
Novak
Ivana
I
Dikic
Ivan
I
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D001343:Autophagy / Q000502:physiology*; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008928:Mitochondria / Q000378:metabolism; D020675:Peroxisomes / Q000378:metabolism; D010588:Phagosomes / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D021381:Protein Transport; D011506:Proteins / Q000378:metabolism; D012270:Ribosomes / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*; D054875:Ubiquitination
D048868:Adaptor Proteins, Signal Transducing; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; C549756:NBR1 protein, human; D011506:Proteins; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex; C433811:HDAC6 protein, human; D000073864:Histone Deacetylase 6; D006655:Histone Deacetylases