SUMOylation Attenuates Human β-Arrestin 2 Inhibition of IL-1R/TRAF6 Signaling

Xiao, Ning; Li, Hui; Mei, Wenhan; Cheng, Jinke

doi:10.1074/jbc.m114.608703

Cited by 18 publications

(13 citation statements)

References 30 publications

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“…Of the SUMO proteins, only SUMO-1 contains a nuclear localization signal that functions by transporting the cargo protein into the nucleus. Interestingly, SUMOylation of β-arrestin 2 attenuates binding to TRAF6, enhancing TRAF6 oligomerization and autoubiquitination [ 96 ]. The adaptor protein p62 is also found to contain a binding site for TRAF6 [ 34 ].…”

Section: Potential Roles Of Sumo-1 In α-Synuclein Aggregation Degmentioning

confidence: 99%

Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity

et al. 2015

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α-Synuclein inclusion bodies are a pathological hallmark of several neurodegenerative diseases, including Parkinson’s disease, and contain aggregated α-synuclein and a variety of recruited factors, including protein chaperones, proteasome components, ubiquitin and the small ubiquitin-like modifier, SUMO-1. Cell culture and animal model studies suggest that misfolded, aggregated α-synuclein is actively translocated via the cytoskeletal system to a region of the cell where other factors that help to lessen the toxic effects can also be recruited. SUMO-1 covalently conjugates to various intracellular target proteins in a way analogous to ubiquitination to alter cellular distribution, function and metabolism and also plays an important role in a growing list of cellular pathways, including exosome secretion and apoptosis. Furthermore, SUMO-1 modified proteins have recently been linked to cell stress responses, such as oxidative stress response and heat shock response, with increased SUMOylation being neuroprotective in some cases. Several recent studies have linked SUMOylation to the ubiquitin-proteasome system, while other evidence implicates the lysosomal pathway. Other reports depict a direct mechanism whereby sumoylation reduced the aggregation tendency of α-synuclein, and reduced the toxicity. However, the precise role of SUMO-1 in neurodegeneration remains unclear. In this review, we explore the potential direct or indirect role(s) of SUMO-1 in the cellular response to misfolded α-synuclein in neurodegenerative disorders.

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Section: Potential Roles Of Sumo-1 In α-Synuclein Aggregation Degmentioning

confidence: 99%

Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity

et al. 2015

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“…Consequently, cytokine production was enhanced in β-arrestin2 deficient BMDMs, in response to TLR4, TLR3 and TLR9 ligands 85 . Recentlly, this interaction of β-arrestin2 with TRAF6 itself has been shown to be regulated by SUMOylation at lysine 295 residue that reduces its affinity for TRAF6 thereby, enhancing signaling through the latter 88 . Consistent with effects in response to TLR ligands, cytokine production to adenovirus infection has been found to be modulated differentially by β-arrestins as demonstrated in both in vivo and in vitro studies 89 .…”

Section: G-protein Coupled Receptorsmentioning

confidence: 99%

Multifaceted role of β-arrestins in inflammation and disease

Sharma

Parameswaran

2015

Genes Immun

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Arrestins are intracellular scaffolding proteins known to regulate a range of biochemical processes including G-protein coupled receptor (GPCR) desensitization, signal attenuation, receptor turnover and downstream signaling cascades. Their roles in regulation of signaling network have lately been extended to receptors outside of the GPCR family, demonstrating their roles as important scaffolding proteins in various physiological processes including proliferation, differentiation, and apoptosis. Recent studies have demonstrated a critical role for arrestins in immunological processes including key functions in inflammatory signaling pathways. In this review, we provide a comprehensive analysis of the different functions of the arrestin family of proteins especially related to immunity and inflammatory diseases.

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“…The immunoprecipitation and Western blot protocols used have been previously described (3). Proteins of interest were detected using the following antibodies: SENP1 (A302-927A; Bethyl Laboratories, Montgomery, TX, USA) and MEKK1 (A302-395A; Bethyl Laboratories); SENP2 (PA5-75184; Thermo Fisher Scientific); FLAG M2 Affinity Gel (A2220; MilliporeSigma) and anti-FLAG M2 (F3165); HA-Tag (66006-1-Ig; Proteintech, Rosemont, IL, USA) and Myc-Tag (66004-1-Ig); NDR1 (H00011329-PW1; Abnova, Taipei, Taiwan) and NDR2 (H00023012-B01P; Abnova); GFP-Tag (S2038; Abcam, Cambridge, United Kingdom); p38 (#8690), phospho-p38 (#4511), ERK1/2 (#4695), phospho-ERK1/ 2 (#4376), MEKK2 (#19607), SAPK/Erk kinase 1 (SEK1) (#9152), phospho-SEK1 (#4514), IkBa (#4814), phospho-IkBa (#2859), and SUMO1 (#4930) (Cell Signaling Technology, Dallas, TX, USA).…”

Section: Immunoprecipitation and Immunoblottingmentioning

confidence: 99%

“…Of note, the directed migration of keratinocytes is the most crucial; defects in this function are often associated with the clinical phenotypes of chronic nonhealing wounds (1). SUMOylation is a widespread and tightly controlled posttranslational modification in regulating various protein functions such as localization, activity, and protein-protein interaction (2,3). It is essentially an enzymatic cascade process that requires small ubiquitin-like modifier (SUMO)-specific E1-activating enzyme, E2-conjugating enzyme, and sometimes E3-ligase, to covalently attach SUMOs to the lysine (K) residues of proteins.…”

mentioning

confidence: 99%

SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation

Xiao

et al. 2018

The FASEB Journal

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A key member of the sentrin/small ubiquitin‐like modifier (SUMO)‐specific protease (SENP) family, SENP2 has been shown to implicate embryonic development, fatty acid metabolism, atherosclerosis, and neurodegenerative diseases. However, other biologic functions of SENP2 and its specific targets are incompletely understood. Here, we uncovered a novel role of SENP2 in negative regulation of keratinocyte migration, a process crucial to wound epithelialization. Defects in this function are often associated with the clinical phenotypes of chronic nonhealing wounds. Mechanistically, SENP2 as a specific de‐SUMOylase targets NDR1 (nuclear Dbf2‐related 1), also called STK38 (serine‐threonine kinase 38), for de‐SUMOylation and SUMO conjugation of NDR1 on Lys‐465 attenuates its inhibition of p38/ERK1/2 activation by decreasing the association of NDR1 with MEK kinase 1/2. Significantly, low‐level laser (LLL) irradiation increases NDR1 SUMOylation and subsequent p38/ERK1/2 activation via down‐regulation of SENP2, leading to faster keratinocyte migration. Our findings fill the gaps that linger in the basic mechanisms underlying LLL therapy.—Xiao, N., Li, H., Yu, W., Gu, C., Fang, H., Peng, Y., Mao, H., Fang, Y., Ni, W., Yao, M.SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation. FASEB J. 33, 163–174 (2019). http://www.fasebj.org

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SUMOylation Attenuates Human β-Arrestin 2 Inhibition of IL-1R/TRAF6 Signaling

Cited by 18 publications

References 30 publications

Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity

Direct and/or Indirect Roles for SUMO in Modulating Alpha-Synuclein Toxicity

Multifaceted role of β-arrestins in inflammation and disease

SUMO‐specific protease 2 (SENP2) suppresses keratinocyte migration by targeting NDR1 for de‐SUMOylation

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