TY  - JOUR
A1  - Tolay, Nazife
A1  - Buchberger, Alexander
T1  - Role of the ubiquitin system in stress granule metabolism
JF  - International Journal of Molecular Sciences
N2  - Eukaryotic cells react to various stress conditions with the rapid formation of membrane-less organelles called stress granules (SGs). SGs form by multivalent interactions between RNAs and RNA-binding proteins and are believed to protect stalled translation initiation complexes from stress-induced degradation. SGs contain hundreds of different mRNAs and proteins, and their assembly and disassembly are tightly controlled by post-translational modifications. The ubiquitin system, which mediates the covalent modification of target proteins with the small protein ubiquitin (‘ubiquitylation’), has been implicated in different aspects of SG metabolism, but specific functions in SG turnover have only recently emerged. Here, we summarize the evidence for the presence of ubiquitylated proteins at SGs, review the functions of different components of the ubiquitin system in SG formation and clearance, and discuss the link between perturbed SG clearance and the pathogenesis of neurodegenerative disorders. We conclude that the ubiquitin system plays an important, medically relevant role in SG biology.
KW  - 26S proteasome
KW  - p97/VCP
KW  - Cdc48
KW  - DUB
KW  - G3BP
KW  - granulostasis
KW  - granulophagy
KW  - ALS
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284061
SN  - 1422-0067
VL  - 23
IS  - 7
ER  - 
TY  - JOUR
A1  - Tolay, Nazife
A1  - Buchberger, Alexander
T1  - Comparative profiling of stress granule clearance reveals differential contributions of the ubiquitin system
JF  - Life Science Alliance
N2  - Stress granules (SGs) are cytoplasmic condensates containing untranslated mRNP complexes. They are induced by various proteotoxic conditions such as heat, oxidative, and osmotic stress. SGs are believed to protect mRNPs from degradation and to enable cells to rapidly resume translation when stress conditions subside. SG dynamics are controlled by various posttranslationalmodifications, but the role of the ubiquitin system has remained controversial. Here, we present a comparative analysis addressing the involvement of the ubiquitin system in SG clearance. Using high-resolution immuno-fluorescence microscopy, we found that ubiquitin associated to varying extent with SGs induced by heat, arsenite, H2O2, sorbitol, or combined puromycin and Hsp70 inhibitor treatment. SG-associated ubiquitin species included K48- and K63-linked conjugates, whereas free ubiquitin was not significantly enriched. Inhibition of the ubiquitin activating enzyme, deubiquitylating enzymes, the 26S proteasome and p97/VCP impaired the clearance of arsenite- and heat-induced SGs, whereas SGs induced by other stress conditions were little affected. Our data underline the differential involvement of the ubiquitin system in SG clearance, a process important to prevent the formation of disease-linked aberrant SGs.
KW  - phase transition
KW  - quality control
KW  - protein
KW  - inhibition
KW  - complexity
KW  - separation
KW  - diversity
KW  - autophagy
KW  - ALS
KW  - P97
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-259810
VL  - 4
IS  - 5
ER  -