Abstract:
:Ubiquitin-specific protease 14 (USP14), one of three proteasome-associated deubiquitinating enzymes, has multifunctional roles in cellular context. Here, we report a novel molecular mechanism and function of USP14 in regulating autophagy induction and nuclear factor-kappa B (NF-κB) activation induced by toll-like receptor (TLR) 4 (TLR4). USP14 interacted with tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) and interrupted the association of Beclin 1 with TRAF6, leading to inhibition of TRAF6-mediated ubiquitination of Beclin 1. Reduced expression of USP14 in USP14-knockdown (USP14KD) THP-1 cells enhanced autophagy induction upon TLR4 stimulation as shown by the increased conversion of cytosolic LC3-I to membrane-bound LC3-II. Moreover, USP14KD human breast carcinoma MDA-MB-231 cells and USP14KD human hepatic adenocarcinoma SK-HEP-1 cells showed increased cell migration and invasion, indicating that USP14 is negatively implicated in the cancer progression by the inhibition of autophagy induction. Furthermore, we found that USP14 interacted with TAK1-binding protein (TAB) 2 protein and induced deubiquitination of TAB 2, a key factor in the activation of NF-κB. Functionally, overexpression of USP14 suppressed TLR4-induced activation of NF-κB. In contrast, USP14KD THP-1 cells showed enhanced activation of NF-κB, NF-κB-dependent gene expression, and production of pro-inflammatory cytokines such as IL-6, IL-1β, and tumor necrosis factor-α. Taken together, our data demonstrate that USP14 can negatively regulate autophagy induction by inhibiting Beclin 1 ubiquitination, interrupting association between TRAF6 and Beclin 1, and affecting TLR4-induced activation of NF-κB through deubiquitination of TAB 2 protein.
journal_name
Front Immunoljournal_title
Frontiers in immunologyauthors
Min Y,Lee S,Kim MJ,Chun E,Lee KYdoi
10.3389/fimmu.2017.01827subject
Has Abstractpub_date
2017-12-15 00:00:00pages
1827issn
1664-3224journal_volume
8pub_type
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journal_title:Frontiers in immunology
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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pub_type: 杂志文章,评审
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2019.01321
更新日期:2019-06-12 00:00:00
abstract::Background: The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has posed great threat to human health. T cells play a critical role in antiviral immunity but their numbers and functional state in COVID-19 patients remain largely unclear. Methods: ...
journal_title:Frontiers in immunology
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doi:10.3389/fimmu.2020.00827
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pub_type: 杂志文章,评审
doi:10.3389/fimmu.2016.00594
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journal_title:Frontiers in immunology
pub_type: 杂志文章
doi:10.3389/fimmu.2016.00553
更新日期:2016-12-05 00:00:00
abstract:Purpose:Patients with juvenile idiopathic arthritis (JIA) are prone to developing chronic anterior uveitis (JIA-U+). Although several risk factors for JIA-U+ have been identified, the underlying etiology is poorly understood. Histopathological studies demonstrate B cell infiltrates in eye tissues of patients with JIA-U...
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