scholarly journals Open-gate mutants of the mammalian proteasome show enhanced ubiquitin-conjugate degradation

2016 ◽  
Vol 7 (1) ◽  
Author(s):  
Won Hoon Choi ◽  
Stefanie A. H. de Poot ◽  
Jung Hoon Lee ◽  
Ji Hyeon Kim ◽  
Dong Hoon Han ◽  
...  
Keyword(s):  
Ubiquitin Conjugate

scholarly journals UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells

2018 ◽  
Vol 115 (50) ◽  
pp. E11642-E11650 ◽  
Author(s):  
Hyoung Tae Kim ◽  
Alfred L. Goldberg
Keyword(s):  
Protein Degradation ◽  
Atp Hydrolysis ◽  
Deubiquitinating Enzyme ◽  
Wild Type ◽  
Peptide Hydrolysis ◽  
Ubiquitin Chain ◽  
Important Regulator ◽  
General Response ◽  
Ubiquitin Conjugate ◽  
Stimulation Of

The best-known function of ubiquitin-like (UBL) domains in proteins is to enable their binding to 26S proteasomes. The proteasome-associated deubiquitinating enzyme Usp14/UBP6 contains an N-terminal UBL domain and is an important regulator of proteasomal activity. Usp14 by itself represses multiple proteasomal activities but, upon binding a ubiquitin chain, Usp14 stimulates these activities and promotes ubiquitin-conjugate degradation. Here, we demonstrate that Usp14’s UBL domain alone mimics this activation of proteasomes by ubiquitin chains. Addition of this UBL domain to purified 26S proteasomes stimulated the same activities inhibited by Usp14: peptide entry and hydrolysis, protein-dependent ATP hydrolysis, deubiquitination by Rpn11, and the degradation of ubiquitinated and nonubiquitinated proteins. Thus, the binding of Usp14’s UBL (apparently to Rpn1’s T2 site) seems to mediate the activation of proteasomes by ubiquitinated substrates. However, the stimulation of these various activities was greater in proteasomes lacking Usp14 than in wild-type particles and thus is a general response that does not involve some displacement of Usp14. Furthermore, the UBL domains from hHR23 and hPLIC1/UBQLN1 also stimulated peptide hydrolysis, and the expression of hHR23A’s UBL domain in HeLa cells stimulated overall protein degradation. Therefore, many UBL-containing proteins that bind to proteasomes may also enhance allosterically its proteolytic activity.

scholarly journals A Subcomplex of the Proteasome Regulatory Particle Required for Ubiquitin-Conjugate Degradation and Related to the COP9-Signalosome and eIF3

Cell ◽  
1998 ◽  
Vol 94 (5) ◽  
pp. 615-623 ◽  
Author(s):  
Michael H Glickman ◽  
David M Rubin ◽  
Olivier Coux ◽  
Inge Wefes ◽  
Günter Pfeifer ◽  
...  
Keyword(s):  
Cop9 Signalosome ◽  
Regulatory Particle ◽  
Ubiquitin Conjugate

scholarly journals Ubiquitin in Motion: Structural Studies of the Ubiquitin-Conjugating Enzyme∼Ubiquitin Conjugate

Biochemistry ◽  
2011 ◽  
Vol 50 (10) ◽  
pp. 1624-1633 ◽  
Author(s):  
Jonathan N. Pruneda ◽  
Kate E. Stoll ◽  
Laura J. Bolton ◽  
Peter S. Brzovic ◽  
Rachel E. Klevit
Keyword(s):  
Structural Studies ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Conjugate ◽  
Conjugating Enzyme

Ubiquitin conjugate immunoreactivity in the brains of scrapie infected mice

1990 ◽  
Vol 162 (1) ◽  
pp. 61-66 ◽  
Author(s):  
James Lowe ◽  
Helen McDermott ◽  
Nigel Kenward ◽  
Michael Landon ◽  
R. John Mayer ◽  
...  
Keyword(s):  
Ubiquitin Conjugate

scholarly journals Exposure of Mesenchymal Stem Cells to an Alzheimer’s Disease Environment Enhances Therapeutic Effects

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Sang Eon Park ◽  
Hyeong Seop Kim ◽  
Soo Jin Kwon ◽  
Min-Jeong Kim ◽  
Suk-joo Choi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Stem Cells ◽  
Cell Death ◽  
Mesenchymal Stem Cells ◽  
Amyloid Beta ◽  
Therapeutic Effects ◽  
Human Mscs ◽  
Sequencing Data ◽  
Ubiquitin Conjugate

Mesenchymal stem cells (MSCs) have emerged as a promising tool for the treatment of Alzheimer’s disease (AD). Previous studies suggested that the coculture of human MSCs with AD in an in vitro model reduced the expression of amyloid-beta 42 (Aβ42) in the medium as well as the overexpression of amyloid-beta- (Aβ-) degrading enzymes such as neprilysin (NEP). We focused on the role of primed MSCs (human Wharton’s jelly-derived mesenchymal stem cells (WJ-MSCs) exposed to an AD cell line via a coculture system) in reducing the levels of Aβ and inhibiting cell death. We demonstrated that mouse groups treated with naïve MSCs and primed MSCs showed significant reductions in cell death, ubiquitin conjugate levels, and Aβ levels, but the effects were greater in primed MSCs. Also, mRNA sequencing data analysis indicated that high levels of TGF-β induced primed-MSCs. Furthermore, treatment with TGF-β reduced Aβ expression in an AD transgenic mouse model. These results highlighted AD environmental preconditioning is a promising strategy to reduce cell death and ubiquitin conjugate levels and maintain the stemness of MSCs. Further, these data suggest that human WJ-MSCs exposed to an AD environment may represent a promising and novel therapy for AD.

scholarly journals Hypoxia—Ischemia Induces a Rapid Elevation of Ubiquitin Conjugate Levels and Ubiquitin Immunoreactivity in the Immature Rat Brain

1998 ◽  
Vol 18 (4) ◽  
pp. 376-385 ◽  
Author(s):  
Susan J. Vannucci ◽  
Rosemary Mummery ◽  
Richard B. Hawkes ◽  
Christopher C. Rider ◽  
Philip W. Beesley
Keyword(s):  
Rat Brain ◽  
Control Level ◽  
Artery Ligation ◽  
Western Blots ◽  
Immature Rat ◽  
Carotid Artery Ligation ◽  
Hypoxia Ischemia ◽  
The Right ◽  
Ubiquitin Conjugate ◽  
Postnatal Rats

Postnatal rats at 7 and 21 days of age were subjected to unilateral hypoxia—ischemia (H/I) by right carotid artery ligation followed by 1.5 to 2 hours of hypoxia (8% oxygen). Brains were frozen at specific intervals of recovery from 0 to 24 hours. Western blots of samples of right and left forebrain were immunodeveloped with a monoclonal antibody specific for ubiquitin, RHUb 1. An elevation of ubiquitin conjugate levels in the right compared with the left forebrain of 7-day-old animals was detectable immediately following H/I and increased by close to 60% of control level within 1 hour of recovery. The conjugate immunoreactivity remained at this level for 6 hours but had declined to control levels by 24 hours of recovery. No such increase was observed in response to hypoxia alone. Similar changes were observed in samples from the 21-day-old rat brain. However, the elevation of ubiquitin conjugate levels was of slower onset and persisted longer than observed for the 7-day-old animals. Immunocytochemical studies of brain fixed by immersion in formaldehyde/acetone/methanol showed that ubiquitin-like immunoreactivity was increased in the right, but not left, cerebral cortex and hippocampus of animals subjected to H/I. The data suggest that elevated ubiquitination may represent a neuroprotective response to H/I.

Activation of the ubiquitin pathway in rat skeletal muscle by catabolic doses of glucocorticoids

1997 ◽  
Vol 272 (3) ◽  
pp. C1007-C1016 ◽  
Author(s):  
D. Auclair ◽  
D. R. Garrel ◽  
A. Chaouki Zerouala ◽  
L. H. Ferland
Keyword(s):  
Skeletal Muscle ◽  
Muscular Atrophy ◽  
Specific Marker ◽  
Rat Skeletal Muscle ◽  
Mrna Accumulation ◽  
Ubiquitin Pathway ◽  
Subunit Mrna ◽  
Muscle Types ◽  
Two Peaks ◽  
Ubiquitin Conjugate

To evaluate whether catabolic levels of glucocorticoids activate the ubiquitin pathway in conjunction with their known proteolytic effect in skeletal muscle, rats were injected daily with corticosterone (CTC; 10 mg/100 g body wt) for 7 days. Two peaks of urinary excretion of 3-methylhistidine (3-MH), a specific marker of myofibrillar proteolysis, were observed at days 1 and 3 (165 and 295% of controls, respectively). Levels of ubiquitin pathway mRNAs in skeletal muscle were assessed around the 3-MH peaks. In the extensor digitorum longus, a first rise of two polyubiquitin (pUb) mRNAs was seen at day 1 (183 and 162% of control for the UbB and UbC transcripts, respectively, P < 0.01). An accumulation of both E2-14k mRNAs (140%, P < 0.02, and 157% of controls, P < 0.01) and proteasome C8 subunit mRNA (222% of control, P < 0.05) was seen at day 2. A second more important peak of induction of pUb mRNA was seen at day 3 (251 and 217% of controls for the UbB and UbC transcripts, respectively, P< 0.001). All transcripts returned to near control levels by day 4. In the soleus, induction of E2-14k mRNA started at day 3 and reached 216 and 208% of controls at day 4 (P < 0.001), whereas an increase of pUb mRNA was observed at days 3 (213 and 241%, P < 0.05) and 4 (211 and 221%, P < 0.001). A rise of proteasome C8 subunit mRNA accumulation was also seen in the soleus at days 3 (217%, P< 0.05) and 4 (157%, P < 0.05). Reduced ubiquitin conjugate levels, possibly due to their rapid degradation through increased proteasome activity, were observed in both muscle types at day 3. The parallel between the catabolic effects of CTC and activation of the ubiquitin pathway in muscles of CTC-treated rats strongly suggests the involvement of this system in glucocorticoid-induced muscular atrophy.

scholarly journals Crystal Structure of a Ube2S-Ubiquitin Conjugate

PLoS ONE ◽  
2016 ◽  
Vol 11 (2) ◽  
pp. e0147550 ◽  
Author(s):  
Sonja Lorenz ◽  
Moitrayee Bhattacharyya ◽  
Christian Feiler ◽  
Michael Rape ◽  
John Kuriyan
Keyword(s):  
Crystal Structure ◽  
Ubiquitin Conjugate

scholarly journals The HIP2~Ubiquitin Conjugate Forms a Non-Compact Monomeric Thioester during Di-Ubiquitin Synthesis

PLoS ONE ◽  
2015 ◽  
Vol 10 (3) ◽  
pp. e0120318 ◽  
Author(s):  
Benjamin W. Cook ◽  
Kathryn R. Barber ◽  
Brian H. Shilton ◽  
Gary S. Shaw
Keyword(s):  
Ubiquitin Conjugate
Sign in / Sign up

Export Citation Format

Share Document