Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation

Liu, Ningning; Kong, Tianyu; Chen, Xiaohua; Hu, Huan; Gu, Hongjiao; Liu, Shiming; Chen, Xiaohui; Li, Aiqun; Xiong, Xuming; Zhang, Zhenhui

doi:10.1007/s11010-017-2978-0

Cited by 37 publications

(39 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Usp14 activity is elevated in LPS-treated-cells, in parallel with its phosphorylation, possibly by AKT [74,75]. These and other observations suggest an anti-inflammatory effect of Usp14 inhibition [74–78]. …”

Section: Enzymatic Activity and Its Regulationmentioning

confidence: 88%

See 1 more Smart Citation

Meddling with Fate: The Proteasomal Deubiquitinating Enzymes

Poot

Tian

Finley

2017

Journal of Molecular Biology

102

115

View full text Add to dashboard Cite

Three deubiquitinating enzymes–Rpn11, Usp14, and Uch37–are associated with the proteasome regulatory particle. These enzymes allow proteasomes to remove ubiquitin from substrates before they are translocated into the core particle to be degraded. Although the translocation channel is too narrow for folded proteins, the force of translocation unfolds them mechanically. As translocation proceeds, ubiquitin chains bound to substrate are drawn to the channel’s entry port, where they can impede further translocation. Rpn11, situated over the port, can remove these chains without compromising degradation because substrates must be irreversibly committed to degradation before Rpn11 acts. This coupling between deubiquitination and substrate degradation is ensured by the Ins-1 loop of Rpn11, which controls ubiquitin access to its catalytic site. In contrast to Rpn11, Usp14 and Uch37 can rescue substrates from degradation by promoting substrate dissociation from the proteasome prior to the commitment step. Uch37 is unique in being a component of both the proteasome and a second multisubunit assembly, the INO80 complex. However, only recruitment into the proteasome activates Uch37. Recruitment to the proteasome likewise activates Usp14. However, the influence of Usp14 on the proteasome depends on the substrate, due to its marked preference for proteins that carry multiple ubiquitin chains. Usp14 exerts complex control over the proteasome, suppressing proteasome activity even when inactive in deubiquitination. A major challenge for the field will be to elucidate the specificities of Rpn11, Usp14, and Uch37 in greater depth, employing not only model in vitro substrates, but their endogenous targets.

show abstract

Section: Enzymatic Activity and Its Regulationmentioning

confidence: 88%

“…Experiments in various model systems have revealed a multitude of processes in which Usp14 and Ubp6 may function [31–33,45,47,48,50,76–78,90,91,93,109,113,127–138]. An interesting phenotype of ubp6 null mutants in yeast is their exceptional and perhaps unique ability to tolerate aneuploid chromosomes [135–137].…”

Section: Physiological Functionmentioning

confidence: 99%

Meddling with Fate: The Proteasomal Deubiquitinating Enzymes

Poot

Tian

Finley

2017

Journal of Molecular Biology

102

115

View full text Add to dashboard Cite

show abstract

“…Our previous studies have shown that USP14 stabilizes AR protein expression by removing the K48 ubiquitin chain on AR in prostate cancer cells and breast cancer cells. Moreover, except for in cancer cells, we also found that USP14 regulates the progression of cardiac hypertrophy via promoting GSK‐3β phosphorylation and USP14 mediates LPS‐induced inflammation by activating ERK1/2 and NF‐κB pathways . However, the function of USP14 in the development of atherosclerosis remains unknown.…”

Section: Discussionmentioning

confidence: 86%

“…USP14 can reduce the anchoring time of ubiquitin conjugates and stabilize the proteins via inducing deubiquitination of proteins . Moreover, in our previous study, we have reported that USP14 was involved in inflammatory diseases by increasing ERK1/2 phosphorylation and NF‐κB activation …”

Section: Introductionmentioning

confidence: 95%

“…21 Moreover, in our previous study, we have reported that USP14 was involved in inflammatory diseases by increasing ERK1/2 phosphorylation and NF-κB activation. 22 In this study, we sought to explore whether USP14 mediates lipid uptake and foam cell formation. Because of the importance of CD36 in the cellular oxLDL uptake and the development of AS, we investigated if CD36 expression is regulated by USP14 and also attempted to study the involved mechanisms in RAW264.7 and THP1 cells.…”

mentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of USP14 suppresses the formation of foam cell by promoting CD36 degradation

Zhang

Xia

Chai

et al. 2020

J Cellular Molecular Medi

Self Cite

View full text Add to dashboard Cite

Atherosclerosis is regarded as a chronic progressive inflammatory disease and is a basic pathophysiological process in coronary artery disease which is life threatening in clinic. The formation of foam cell plays a key role in the pathogenesis of atherosclerosis. OxLDL is a significant factor in progression of coronary artery disease. Our studies have demonstrated that USP14 promotes cancer development and mediates progression of cardiac hypertrophy and LPS‐induced inflammation. However, the underlying mechanism of USP14 is unknown. In this study, we found that the inhibition of USP14 significantly suppressed the oxLDL uptake, subsequently decreased the foam cell formation. Surprisingly, USP14 has an effect on the expression of CD36 but not SR‐A, ABCA1, Lox‐1, ABCG1 and SR‐Bl. Furthermore, USP14 stabilizes CD36 protein via cleaving the ubiquitin chain on CD36. Blocking CD36 activation using antibody‐dependent blocking assay remarkably attenuated the function of USP14 on the formation of foam cell. In summary, our results suggested that the inhibition of USP14 decreases foam cell formation by down‐regulating CD36‐mediated lipid uptake and provides a potential therapeutic target for atherosclerosis.

show abstract

Cai's Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10

Zhu

Zhang

et al. 2018

Biotech and App Biochem

View full text Add to dashboard Cite

To observe the effect of Cai's Neiyi Prescription (CNYP) on the apoptosis and inflammation in endometrial stromal cells with endometriosis (EM) both in vivo and in vitro, EM model rats and endometrial stromal cells were treated with CNYP and the level of USP10, p-ERK1/2, ERK1/2, and apoptosis-related protein as well as the levels of proinflammatory factors were measured by Western blotting and ELISA, respectively. Rats with surgically induced EM showed increased USP10 expression and ERK/2 activation. Intragastric administration of CNYP granule significantly inhibited EM-induced ERK1/2 activation and expression of USP10 and Bcl-2, but increased the expression of Bax and Caspase-7 in EM-induced rats. CNYP granule administration also inhibited EM-induced inflammation in rats. Moreover, the ectopic endometrial stromal cells isolated from EM patients demonstrated decreased ERK1/2 activation and expression of USP10 and Bcl-2 and increased expression of Bax and Caspase-7 after cultured in DMEM containing CNYP-medicated rat serum, which were reversed by USP10 overexpression and were enhanced by USP10 siRNA. USP10 overexpression also inhibited while USP10 siRNA enhanced the CNYP-induced inhibition of inflammation in ectopic endometrial stromal cells. Taken together, our results suggest that CNYP granule promotes apoptosis and inhibits inflammation in endometrial stromal cells with EM through inhibiting USP10. C 2018

show abstract

Ubiquitin-specific protease 14 regulates LPS-induced inflammation by increasing ERK1/2 phosphorylation and NF-κB activation

Cited by 37 publications

References 30 publications

Meddling with Fate: The Proteasomal Deubiquitinating Enzymes

Meddling with Fate: The Proteasomal Deubiquitinating Enzymes

Inhibition of USP14 suppresses the formation of foam cell by promoting CD36 degradation

Cai's Neiyi Prescription promotes apoptosis and inhibits inflammation in endometrial stromal cells with endometriosis through inhibiting USP10

Contact Info

Product

Resources

About