Full Text:   <849>

Summary:  <109>

Suppl. Mater.: 

CLC number: 

On-line Access: 2024-03-01

Received: 2023-06-11

Revision Accepted: 2023-08-03

Crosschecked: 2024-03-06

Cited: 0

Clicked: 620

Citations:  Bibtex RefMan EndNote GB/T7714

-   Go to

Article info.
Open peer comments

Journal of Zhejiang University SCIENCE B 2024 Vol.25 No.3 P.212-232

http://doi.org/10.1631/jzus.B2300403


Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells


Author(s):  Hong CAO, Xuchang ZHOU, Bowen XU, Han HU, Jianming GUO, Yuwei MA, Miao WANG, Nan LI, Jun ZOU

Affiliation(s):  Department of Sport Rehabilitation, Shanghai University of Sport, Shanghai 200438, China; more

Corresponding email(s):   junzou@sus.edu.cn, linan@immunol.org

Key Words:  Endoplasmic reticulum-associated degradation (ERAD), Protein folding, Ubiquitination, Retrotranslocation


Hong CAO, Xuchang ZHOU, Bowen XU, Han HU, Jianming GUO, Yuwei MA, Miao WANG, Nan LI, Jun ZOU. Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells[J]. Journal of Zhejiang University Science B, 2024, 25(3): 212-232.

@article{title="Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells",
author="Hong CAO, Xuchang ZHOU, Bowen XU, Han HU, Jianming GUO, Yuwei MA, Miao WANG, Nan LI, Jun ZOU",
journal="Journal of Zhejiang University Science B",
volume="25",
number="3",
pages="212-232",
year="2024",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B2300403"
}

%0 Journal Article
%T Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells
%A Hong CAO
%A Xuchang ZHOU
%A Bowen XU
%A Han HU
%A Jianming GUO
%A Yuwei MA
%A Miao WANG
%A Nan LI
%A Jun ZOU
%J Journal of Zhejiang University SCIENCE B
%V 25
%N 3
%P 212-232
%@ 1673-1581
%D 2024
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B2300403

TY - JOUR
T1 - Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells
A1 - Hong CAO
A1 - Xuchang ZHOU
A1 - Bowen XU
A1 - Han HU
A1 - Jianming GUO
A1 - Yuwei MA
A1 - Miao WANG
A1 - Nan LI
A1 - Jun ZOU
J0 - Journal of Zhejiang University Science B
VL - 25
IS - 3
SP - 212
EP - 232
%@ 1673-1581
Y1 - 2024
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B2300403


Abstract: 
The endoplasmic reticulum is a key site for protein production and quality control. More than one-third of proteins are synthesized and folded into the correct three-dimensional conformation in the endoplasmic reticulum. However, during protein folding, unfolded and/or misfolded proteins are prone to occur, which may lead to endoplasmic reticulum stress. Organisms can monitor the quality of the proteins produced by endoplasmic reticulum quality control (ERQC) and endoplasmic reticulum-associated degradation (ERAD), which maintain endoplasmic reticulum protein homeostasis by degrading abnormally folded proteins. The underlying mechanisms of protein folding and ERAD in mammals have not yet been fully explored. Therefore, this paper reviews the process and function of protein folding and ERAD in mammalian cells, in order to help clinicians better understand the mechanism of ERAD and to provide a scientific reference for the treatment of diseases caused by abnormal ERAD.

哺乳动物细胞蛋白质折叠和内质网相关降解的研究进展

曹红1, 2,周绪昌1,徐博文2,胡涵2,郭健民1,马誉玮1,王淼1,李楠2,邹军1
1上海体育大学运动健康学院,中国上海市,200438
2海军军医大学,免疫与炎症全国重点实验室,中国上海市,200433
摘要:内质网是体内蛋白质产生和质量控制的关键场所,体内约1/3的蛋白是经内质网合成并加工发挥作用。蛋白质合成后需要进行一定的折叠,形成正确的三维构象,从而发挥其功能。然而在蛋白质折叠过程中易出现错误,导致未折叠和(或)错误折叠蛋白在内质网内聚集,进而导致内质网应激。对此,机体可通过内质网质量控制(ERQC)和内质网相关降解(ERAD)对生成的蛋白质质量进行检测,并通过降解异常折叠蛋白质,以维持内质网内蛋白稳态。目前为止,对哺乳动物体内有关蛋白质折叠和ERAD的详细机制描述尚不全面。为此,本文综述了哺乳动物细胞中蛋白质折叠与ERAD的过程和功能,并重点对ERAD相关蛋白质构象疾病的潜在病理生理学进行了介绍。

关键词:内质网相关降解;蛋白质折叠;泛素化;逆向转位

Darkslateblue:Affiliate; Royal Blue:Author; Turquoise:Article

Reference

[1]AbisambraJF, JinwalUK, BlairLJ, et al., 2013. Tau accumulation activates the unfolded protein response by impairing endoplasmic reticulum-associated degradation. J Neurosci, 33(22):9498-9507.

[2]AlbrechtD, IsenbergAL, StradfordJ, et al., 2020. Associations between vascular function and tau PET are associated with global cognition and amyloid. J Neurosci, 40(44):8573-8586.

[3]AlcockF, SwantonE, 2009. Mammalian OS-9 is upregulated in response to endoplasmic reticulum stress and facilitates ubiquitination of misfolded glycoproteins. J Mol Biol, 385(4):1032-1042.

[4]AlzayadyKJ, PanningMM, KelleyGG, et al., 2005. Involvement of the p97-Ufd1-Npl4 complex in the regulated endoplasmic reticulum-associated degradation of inositol 1,4,5-trisphosphate receptors. J Biol Chem, 280(41):‍34530-34537.

[5]AmanoT, YamasakiS, YagishitaN, et al., 2003. Synoviolin/Hrd1, an E3 ubiquitin ligase, as a novel pathogenic factor for arthropathy. Genes Dev, 17(19):2436-2449.

[6]BagolaK, von DelbrückM, DittmarG, et al., 2013. Ubiquitin binding by a CUE domain regulates ubiquitin chain formation by ERAD E3 ligases. Mol Cell, 50(4):528-539.

[7]BallarP, ShenYX, YangH, et al., 2006. The role of a novel p97/valosin-containing protein-interacting motif of gp78 in endoplasmic reticulum-associated degradation. J Biol Chem, 281(46):35359-35368.

[8]BallarP, OrsAU, YangH, et al., 2010. Differential regulation of CFTRΔF508 degradation by ubiquitin ligases gp78 and Hrd1. Int J Biochem Cell Biol, 42(1):167-173.

[9]BarghoutSH, SchimmerAD, 2021. E1 enzymes as therapeutic targets in cancer. Pharmacol Rev, 73(1):1-56.

[10]BarteeE, MansouriM, Hovey NerenbergBT, et al., 2004. Downregulation of major histocompatibility complex class I by human ubiquitin ligases related to viral immune evasion proteins. J Virol, 78(3):1109-1120.

[11]BernasconiR, GalliC, CalancaV, et al., 2010. Stringent requirement for HRD1, SEL1L, and OS-9/XTP3-B for disposal of ERAD-Ls substrates. J Cell Biol, 188(2):223-235.

[12]BernasconiR, MolinariM, 2011. ERAD and ERAD tuning: disposal of cargo and of ERAD regulators from the mammalian ER. Curr Opin Cell Biol, 23(2):176-183.

[13]BlackwoodEA, MacdonnellLF, ThueraufDJ, et al., 2023. Noncanonical form of ERAD regulates cardiac hypertrophy. Circulation, 147(1):66-82.

[14]BlytheEE, OlsonKC, ChauV, et al., 2017. Ubiquitin- and ATP-dependent unfoldase activity of P97/VCP·NPLOC4·UFD1L is enhanced by a mutation that causes multisystem proteinopathy. Proc Natl Acad Sci USA, 114(22):E4380-E4388.

[15]BonifacinoJS, CossonP, KlausnerRD, 1990. Colocalized transmembrane determinants for ER degradation and subunit assembly explain the intracellular fate of TCR chains. Cell, 63(3):503-513.

[16]BorgoC, D'AmoreC, CapurroV, et al., 2022. Targeting the E1 ubiquitin-activating enzyme (UBA1) improves elexacaftor/tezacaftor/ivacaftor efficacy towards F508del and rare misfolded CFTR mutants. Cell Mol Life Sci, 79(4):192.

[17]BraakmanI, BulleidNJ, 2011. Protein folding and modification in the mammalian endoplasmic reticulum. Annu Rev Biochem, 80:71-99.

[18]CalìT, GalliC, OlivariS, et al., 2008. Segregation and rapid turnover of EDEM1 by an autophagy-like mechanism modulates standard ERAD and folding activities. Biochem Biophys Res Commun, 371(3):405-410.

[19]CaoJ, WangJ, QiW, et al., 2007. Ufd1 is a cofactor of gp78 and plays a key role in cholesterol metabolism by regulating the stability of HMG-CoA reductase. Cell Metab, 6(2):115-128.

[20]CarrierL, 2010. Too much of a good thing is bad: proteasome inhibition induces stressed hearts to fail. Cardiovasc Res, 88(3):389-390.

[21]CarvalhoP, GoderV, RapoportTA, 2006. Distinct ubiquitin-ligase complexes define convergent pathways for the degradation of ER proteins. Cell, 126(2):361-373.

[22]CarvalhoP, StanleyAM, RapoportTA, 2010. Retrotranslocation of a misfolded luminal ER protein by the ubiquitin-ligase Hrd1p. Cell, 143(4):579-591.

[23]ChakrabartiKS, LiJ, DasR, et al., 2017. Conformational dynamics and allostery in E2:E3 interactions drive ubiquitination: gp78 and Ube2g2. Structure, 25(5):‍794-805.e5.

[24]ChenB, MarianoJ, TsaiYC, et al., 2006. The activity of a human endoplasmic reticulum-associated degradation E3, gp78, requires its cue domain, RING finger, and an E2-binding site. Proc Natl Acad Sci USA, 103(2):341-346.

[25]ChenL, MaduraK, 2002. Rad23 promotes the targeting of proteolytic substrates to the proteasome. Mol Cell Biol, 22(13):4902-4913.

[26]ChenQ, ZhongYW, WuYR, et al., 2016. HRD1-mediated ERAD tuning of ER-bound E2 is conserved between plants and mammals. Nat Plants, 2(7):16094.

[27]ChiritoiuM, ChiritoiuGN, MunteanuCVA, et al., 2020. EDEM1 drives misfolded protein degradation via ERAD and exploits ER-phagy as back-up mechanism when ERAD is impaired. Int J Mol Sci, 21(10):3468.

[28]ChouTF, BulferSL, WeihlCC, et al., 2014. Specific inhibition of p97/VCP ATPase and kinetic analysis demonstrate interaction between D1 and D2 ATPase domains. J Mol Biol, 426(15):2886-2899.

[29]ChristiansonJC, ShalerTA, TylerRE, et al., 2008. OS-9 and GRP94 deliver mutant α1-antitrypsin to the Hrd1-SEL1L ubiquitin ligase complex for ERAD. Nat Cell Biol, 10(3):272-282.

[30]ChristiansonJC, OlzmannJA, ShalerTA, et al., 2012. Defining human ERAD networks through an integrative mapping strategy. Nat Cell Biol, 14(1):93-105.

[31]ConnorAM, MahomedN, GandhiR, et al., 2012. TNFα modulates protein degradation pathways in rheumatoid arthritis synovial fibroblasts. Arthritis Res Ther, 14(2):R62.

[32]CrottiL, CelanoG, DagradiF, et al., 2008. Congenital long QT syndrome. Orphanet J Rare Dis, 3:18.

[33]CurranME, SplawskiI, TimothyKW, et al., 1995. A molecular basis for cardiac arrhythmia: HERG mutations cause long QT syndrome. Cell, 80(5):795-803.

[34]DasR, MarianoJ, TsaiYC, et al., 2009. Allosteric activation of E2-RING finger-mediated ubiquitylation by a structurally defined specific E2-binding region of gp78. Mol Cell, 34(6):674-685.

[35]DavisC, SpallerBL, MatouschekA, 2021. Mechanisms of substrate recognition by the 26S proteasome. Curr Opin Struct Biol, 67:161-169.

[36]DaySM, 2013. The ubiquitin proteasome system in human cardiomyopathies and heart failure. Am J Physiol Heart Circ Physiol, 304(10):H1283-H1293.

[37]DoroudgarS, VölkersM, ThueraufDJ, et al., 2015. Hrd1 and ER-associated protein degradation, ERAD, are critical elements of the adaptive ER stress response in cardiac myocytes. Circ Res, 117(6):536-546.

[38]EiseleMR, ReedRG, RudackT, et al., 2018. Expanded coverage of the 26S proteasome conformational landscape reveals mechanisms of peptidase gating. Cell Rep, 24(5):1301-1315.e5.

[39]ElsasserS, GaliRR, SchwickartM, et al., 2002. Proteasome subunit Rpn1 binds ubiquitin-like protein domains. Nat Cell Biol, 4(9):725-730.

[40]EuraY, YanamotoH, AraiY, et al., 2012. Derlin-1 deficiency is embryonic lethal, Derlin-3 deficiency appears normal, and Herp deficiency is intolerant to glucose load and ischemia in mice. PLoS ONE, 7(3):e34298.

[41]EuraY, MiyataT, KokameK, 2020. Derlin-3 is required for changes in ERAD complex formation under ER stress. Int J Mol Sci, 21(17):6146.

[42]FangSY, FerroneM, YangCH, et al., 2001. The tumor autocrine motility factor receptor, gp78, is a ubiquitin protein ligase implicated in degradation from the endoplasmic reticulum. Proc Natl Acad Sci USA, 98(25):14422-14427.

[43]FeigeMJ, HendershotLM, 2013. Quality control of integral membrane proteins by assembly-dependent membrane integration. Mol Cell, 51(3):297-309.

[44]Fernández-SáizV, BuchbergerA, 2010. Imbalances in p97 co-factor interactions in human proteinopathy. EMBO Rep, 11(6):479-485.

[45]FliermanD, ColemanCS, PickartCM, et al., 2006. E2-25K mediates US11-triggered retro-translocation of MHC class I heavy chains in a permeabilized cell system. Proc Natl Acad Sci USA, 103(31):11589-11594.

[46]FooB, BarbierC, GuoK, et al., 2019. Mutation-specific peripheral and ER quality control of hERG channel cell-surface expression. Sci Rep, 9:6066.

[47]FranciscoAB, SinghR, LiS, et al., 2010. Deficiency of suppressor enhancer Lin12 1 like (SEL1L) in mice leads to systemic endoplasmic reticulum stress and embryonic lethality. J Biol Chem, 285(18):13694-13703.

[48]GaoBX, LeeSM, ChenA, et al., 2008. Synoviolin promotes IRE1 ubiquitination and degradation in synovial fibroblasts from mice with collagen-induced arthritis. EMBO Rep, 9(5):480-485.

[49]GeevasingaN, MenonP, ÖzdinlerPH, et al., 2016. Pathophysiological and diagnostic implications of cortical dysfunction in ALS. Nat Rev Neurol, 12(11):651-661.

[50]GreenblattEJ, OlzmannJA, KopitoRR, 2011. Derlin-1 is a rhomboid pseudoprotease required for the dislocation of mutant α‍-1 antitrypsin from the endoplasmic reticulum. Nat Struct Mol Biol, 18(10):1147-1152.

[51]HagiwaraM, LingJJ, KoenigPA, et al., 2016. Posttranscriptional regulation of glycoprotein quality control in the endoplasmic reticulum is controlled by the E2 Ub-conjugating enzyme UBC6e. Mol Cell, 63(5):753-767.

[52]HamptonRY, GardnerRG, RineJ, 1996. Role of 26S proteasome and HRD genes in the degradation of 3-hydroxy-3-methylglutaryl-CoA reductase, an integral endoplasmic reticulum membrane protein. Mol Biol Cell, 7(12):‍2029-2044.

[53]HannaJ, LeggettDS, FinleyD, 2003. Ubiquitin depletion as a key mediator of toxicity by translational inhibitors. Mol Cell Biol, 23(24):9251-9261.

[54]HantoucheC, WilliamsonB, ValinskyWC, et al., 2017. Bag1 co-chaperone promotes TRC8 E3 ligase-dependent degradation of misfolded human ether a go-go-related gene (hERG) potassium channels. J Biol Chem, 292(6):‍2287-2300.

[55]HassinkG, KikkertM, van VoordenS, et al., 2005. TEB4 is a C4HC3 ring finger-containing ubiquitin ligase of the endoplasmic reticulum. Biochem J, 388(2):647-655.

[56]HebertDN, LamribenL, PowersET, et al., 2014. The intrinsic and extrinsic effects of N-linked glycans on glycoproteostasis. Nat Chem Biol, 10(11):902-910.

[57]HeleniusA, AebiM, 2004. Roles of N-linked glycans in the endoplasmic reticulum. Annu Rev Biochem, 73:1019-1049.

[58]HirschC, BlomD, PloeghHL, 2003. A role for N-glycanase in the cytosolic turnover of glycoproteins. EMBO J, 22(5):1036-1046.

[59]HoriO, IchinodaF, YamaguchiA, et al., 2004. Role of Herp in the endoplasmic reticulum stress response. Genes Cells, 9(5):457-469.

[60]HorimotoS, NinagawaS, OkadaT, et al., 2013. The unfolded protein response transducer ATF6 represents a novel transmembrane-type endoplasmic reticulum-associated degradation substrate requiring both mannose trimming and SEL1L protein. J Biol Chem, 288(44):31517-31527.

[61]HosokawaN, WadaI, 2016. Association of the SEL1L protein transmembrane domain with HRD1 ubiquitin ligase regulates ERAD-L. FEBS J, 283(1):157-172.

[62]HosokawaN, WadaI, NagasawaK, et al., 2008. Human XTP3-B forms an endoplasmic reticulum quality control scaffold with the HRD1-SEL1L ubiquitin ligase complex and BiP. J Biol Chem, 283(30):20914-20924.

[63]IidaY, FujimoriT, OkawaK, et al., 2011. SEL1L protein critically determines the stability of the HRD1-SEL1L endoplasmic reticulum-associated degradation (ERAD) complex to optimize the degradation kinetics of ERAD substrates. J Biol Chem, 286(19):16929-16939.

[64]IshikuraS, WeissmanAM, BonifacinoJS, 2010. Serine residues in the cytosolic tail of the T-cell antigen receptor α‍-chain mediate ubiquitination and endoplasmic reticulum-associated degradation of the unassembled protein. J Biol Chem, 285(31):23916-23924.

[65]IurlaroR, Muñoz-PinedoC, 2016. Cell death induced by endoplasmic reticulum stress. FEBS J, 283(14):2640-2652.

[66]JahnTR, RadfordSE, 2005. The Yin and Yang of protein folding. FEBS J, 272(23):5962-5970.

[67]JiangJH, BallingerCA, WuYX, et al., 2001. CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation. J Biol Chem, 276(46):‍42938-42944.

[68]JohnsonJO, MandrioliJ, BenatarM, et al., 2010. Exome sequencing reveals VCP mutations as a cause of familial ALS. Neuron, 68(5):857-864.

[69]JungES, HongH, KimC, et al., 2015. Acute ER stress regulates amyloid precursor protein processing through ubiquitin-dependent degradation. Sci Rep, 5:8805.

[70]KanekoM, IshiguroM, NiinumaY, et al., 2002. Human HRD1 protects against ER stress-induced apoptosis through ER-associated degradation. FEBS Lett, 532(1-2):‍147-152.

[71]KanekoM, KoikeH, SaitoR, et al., 2010. Loss of HRD1-mediated protein degradation causes amyloid precursor protein accumulation and amyloid-β generation. J Neurosci, 30(11):3924-3932.

[72]KanningKC, KaplanA, HendersonCE, 2010. Motor neuron diversity in development and disease. Annu Rev Neurosci, 33:409-440.

[73]KhouryGA, BalibanRC, FloudasCA, 2011. Proteome-wide post-translational modification statistics: frequency analysis and curation of the Swiss-Prot database. Sci Rep, 1:90.

[74]KikkertM, DoolmanR, DaiM, et al., 2004. Human HRD1 is an E3 ubiquitin ligase involved in degradation of proteins from the endoplasmic reticulum. J Biol Chem, 279(5):3525-3534.

[75]KitykR, KoppJ, MayerMP, 2018. Molecular mechanism of J-domain-triggered ATP hydrolysis by Hsp70 chaperones. Mol Cell, 69(2):227-237.e4.

[76]KleijnenMF, ShihAH, ZhouPB, et al., 2000. The hPLIC proteins may provide a link between the ubiquitination machinery and the proteasome. Mol Cell, 6(2):409-419.

[77]KwonD, KimSM, JacobP, et al., 2019. Induction via functional protein stabilization of hepatic cytochromes P450 upon gp78/autocrine motility factor receptor (AMFR) ubiquitin E3-ligase genetic ablation in mice: therapeutic and toxicological relevance. Mol Pharmacol, 96(5):‍641-654.

[78]LeeJN, SongBL, Debose-BoydRA, et al., 2006. Sterol-regulated degradation of Insig-1 mediated by the membrane-bound ubiquitin ligase gp78. J Biol Chem, 281(51):‍39308-39315.

[79]LeeMJ, LeeBH, HannaJ, et al., 2011. Trimming of ubiquitin chains by proteasome-associated deubiquitinating enzymes. Mol Cell Proteomics, 10(5):R110.003871.

[80]LiGT, ZhouXK, ZhaoG, et al., 2005. Multiple modes of interaction of the deglycosylation enzyme, mouse peptide N-glycanase, with the proteasome. Proc Natl Acad Sci USA, 102(44):15809-15814.

[81]LiGT, ZhaoG, ZhouXK, et al., 2006. The AAA ATPase p97 links peptide N-glycanase to the endoplasmic reticulum-associated E3 ligase autocrine motility factor receptor. Proc Natl Acad Sci USA, 103(22):8348-8353.

[82]LiK, ZhangKN, WangH, et al., 2021. Hrd1-mediated ACLY ubiquitination alleviate NAFLD in db/db mice. Metabolism, 114:154349.

[83]LiangJS, KimT, FangSY, et al., 2003. Overexpression of the tumor autocrine motility factor receptor gp78, a ubiquitin protein ligase, results in increased ubiquitinylation and decreased secretion of apolipoprotein B100 in HepG2 cells. J Biol Chem, 278(26):23984-23988.

[84]LilleyBN, PloeghHL, 2005. Multiprotein complexes that link dislocation, ubiquitination, and extraction of misfolded proteins from the endoplasmic reticulum membrane. Proc Natl Acad Sci USA, 102(40):14296-14301.

[85]Lippincott-SchwartzJ, BonifacinoJS, YuanLC, et al., 1988. Degradation from the endoplasmic reticulum: disposing of newly synthesized proteins. Cell, 54(2):209-220.

[86]LiuWX, ShangYL, LiW, 2014. gp78 elongates of polyubiquitin chains from the distal end through the cooperation of its G2BR and CUE domains. Sci Rep, 4:7138.

[87]LuoWW, LiS, LiC, et al., 2017. iRhom2 is essential for innate immunity to RNA virus by antagonizing ER- and mitochondria-associated degradation of VISA. PLoS Pathog, 13(11):e1006693.

[88]MäättänenP, GehringK, BergeronJJM, et al., 2010. Protein quality control in the ER: the recognition of misfolded proteins. Semin Cell Dev Biol, 21(5):500-511.

[89]McCrackenAA, BrodskyJL, 1996. Assembly of ER-associated protein degradation in vitro: dependence on cytosol, calnexin, and ATP. J Cell Biol, 132(3):291-298.

[90]MeyerH, BugM, BremerS, 2012. Emerging functions of the VCP/p97 AAA-ATPase in the ubiquitin system. Nat Cell Biol, 14(2):117-123.

[91]MiyamotoK, TaguchiY, SaitoK, 2019. Unique RING finger structure from the human HRD1 protein. Protein Sci, 28(2):448-453.

[92]MuellerB, LilleyBN, PloeghHL, 2006. SEL1L, the homologue of yeast Hrd3p, is involved in protein dislocation from the mammalian ER. J Cell Biol, 175(2):261-270.

[93]MuellerB, KlemmEJ, SpoonerE, et al., 2008. SEL1L nucleates a protein complex required for dislocation of misfolded glycoproteins. Proc Natl Acad Sci USA, 105(34):12325-12330.

[94]MüllerJMM, DeinhardtK, RosewellI, et al., 2007. Targeted deletion of p97 (VCP/CDC48) in mouse results in early embryonic lethality. Biochem Biophys Res Commun, 354(2):459-465.

[95]NabiIR, RazA, 1987. Cell shape modulation alters glycosylation of a metastatic melanoma cell-surface antigen. Int J Cancer, 40(3):396-402.

[96]NadavE, ShmueliA, BarrH, et al., 2003. A novel mammalian endoplasmic reticulum ubiquitin ligase homologous to the yeast Hrd1. Biochem Biophys Res Commun, 303(1):‍91-97.

[97]NishitohH, KadowakiH, NagaiA, et al., 2008. ALS-linked mutant SOD1 induces ER stress- and ASK1-dependent motor neuron death by targeting Derlin-1. Genes Dev, 22(11):1451-1464.

[98]NobleW, HangerDP, MillerCC, et al., 2013. The importance of tau phosphorylation for neurodegenerative diseases. Front Neurol, 4:83.

[99]Nowakowska-GołackaJ, CzapiewskaJ, SominkaH, et al., 2021. EDEM1 regulates amyloid precursor protein (APP) metabolism and amyloid-β production. Int J Mol Sci, 23(1):117.

[100]OdaY, OkadaT, YoshidaH, et al., 2006. Derlin-2 and Derlin-3 are regulated by the mammalian unfolded protein response and are required for ER-associated degradation. J Cell Biol, 172(3):383-393.

[101]Okuda-ShimizuY, HendershotLM, 2007. Characterization of an ERAD pathway for nonglycosylated BiP substrates, which require Herp. Mol Cell, 28(4):544-554.

[102]PaganJ, SetoT, PaganoM, et al., 2013. Role of the ubiquitin proteasome system in the Heart. Circ Res, 112(7):‍1046-1058.

[103]PetersOM, GhasemiM, BrownRH, 2015. Emerging mechanisms of molecular pathology in ALS. J Clin Invest, 125(6):2548.

[104]PetersSL, DéryMA, LeblancAC, 2016. Familial prion protein mutants inhibit Hrd1-mediated retrotranslocation of misfolded proteins by depleting misfolded protein sensor BiP. Human Mol Genet, 25(5):976-988.

[105]PetersonBG, GlaserML, RapoportTA, et al., 2019. Cycles of autoubiquitination and deubiquitination regulate the ERAD ubiquitin ligase Hrd1. Elife, 8:e50903.

[106]PfefferS, BurbaumL, UnverdorbenP, et al., 2015. Structure of the native Sec61 protein-conducting channel. Nat Commun, 6:8403.

[107]PickartCM, FushmanD, 2004. Polyubiquitin chains: polymeric protein signals. Curr Opin Chem Biol, 8(6):610-616.

[108]PontingCP, 2000. Proteins of the endoplasmic-reticulum-associated degradation pathway: domain detection and function prediction. Biochem J, 351(2):527-535.

[109]PredmoreJM, WangP, DavisF, et al., 2010. Ubiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies. Circulation, 121(8):997-1004.

[110]PrestonGM, BrodskyJL, 2017. The evolving role of ubiquitin modification in endoplasmic reticulum-associated degradation. Biochem J, 474(4):445-469.

[111]PrintsevI, CurielD, CarrawayKL III, 2017. Membrane protein quantity control at the endoplasmic reticulum. J Membr Biol, 250(4):379-392.

[112]RanekMJ, TerpstraEJM, LiJ, et al., 2013. Protein kinase G positively regulates proteasome-mediated degradation of misfolded proteins. Circulation, 128(4):365-376.

[113]ReggioriF, MonastyrskaI, VerheijeMH, et al., 2010. Coronaviruses hijack the LC3-I-positive EDEMosomes, ER-derived vesicles exporting short-lived ERAD regulators, for replication. Cell Host Microbe, 7(6):500-508.

[114]Reyes-TurcuFE, VentiiKH, WilkinsonKD, 2009. Regulation and cellular roles of ubiquitin-specific deubiquitinating enzymes. Annu Rev Biochem, 78:363-397.

[115]RozeE, SaudouF, CabocheJ, 2008. Pathophysiology of Huntington’s disease: from huntingtin functions to potential treatments. Curr Opin Neurol, 21(4):497-503.

[116]RutkowskiDT, HegdeRS, 2010. Regulation of basal cellular physiology by the homeostatic unfolded protein response. J Cell Biol, 189(5):783-794.

[117]SchuberthC, BuchbergerA, 2008. UBX domain proteins: major regulators of the AAA ATPase Cdc48/p97. Cell Mol Life Sci, 65(15):2360-2371.

[118]SchulzeA, StanderaS, BuergerE, et al., 2005. The ubiquitin-domain protein HERP forms a complex with components of the endoplasmic reticulum associated degradation pathway. J Mol Biol, 354(5):1021-1027.

[119]ShahheydariH, RagagninA, WalkerAK, et al., 2017. Protein quality control and the amyotrophic lateral sclerosis/frontotemporal dementia continuum. Front Mol Neurosci, 10:119.

[120]ShimizuY, Okuda-ShimizuY, HendershotLM, 2010. Ubiquitylation of an ERAD substrate occurs on multiple types of amino acids. Mol Cell, 40(6):917-926.

[121]SickingM, LangS, BochenF, et al., 2021. Complexity and specificity of Sec61-channelopathies: human diseases affecting gating of the Sec61 complex. Cells, 10(5):1036.

[122]SmithJL, AndersonCL, BurgessDE, et al., 2016. Molecular pathogenesis of long QT syndrome type 2. J Arrhythm, 32(5):373-380.

[123]SmithMH, PloeghHL, WeissmanJS, 2011. Road to ruin: targeting proteins for degradation in the endoplasmic reticulum. Science, 334(6059):1086-1090.

[124]SongBL, SeverN, Debose-BoydRA, 2005. Gp78, a membrane-anchored ubiquitin ligase, associates with Insig-1 and couples sterol-regulated ubiquitination to degradation of HMG CoA reductase. Mol Cell, 19(6):829-840.

[125]SowaME, BennettEJ, GygiSP, et al., 2009. Defining the human deubiquitinating enzyme interaction landscape. Cell, 138(2):389-403.

[126]SunSY, ShiGJ, ShaHB, et al., 2015. IRE1α is an endogenous substrate of endoplasmic-reticulum-associated degradation. Nat Cell Biol, 17(12):1546-1555.

[127]SunZH, GuerrieroCJ, BrodskyJL, 2021. Substrate ubiquitination retains misfolded membrane proteins in the endoplasmic reticulum for degradation. Cell Rep, 36(12):109717.

[128]SuzukiM, OtsukaT, OhsakiY, et al., 2012. Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets. Mol Biol Cell, 23(5):800-810.

[129]TanakaK, 2009. The proteasome: overview of structure and functions. Proc Jpn Acad Ser B Phys Biol Sci, 85(1):12-36.

[130]TabataK, ArakawaM, IshidaK, et al., 2021. Endoplasmic reticulum-associated degradation controls virus protein homeostasis, which is required for flavivirus propagation. J Virol, 95(15):e0223420.

[131]TsaiB, YeYH, RapoportTA, 2002. Retro-translocation of proteins from the endoplasmic reticulum into the cytosol. Nat Rev Mol Cell Biol, 3(4):246-255.

[132]TydlackaS, WangCE, WangXJ, et al., 2008. Differential activities of the ubiquitin-proteasome system in neurons versus glia may account for the preferential accumulation of misfolded proteins in neurons. J Neurosci, 28(49):13285-13295.

[133]UshiodaR, HosekiJ, NagataK, 2013. Glycosylation-independent ERAD pathway serves as a backup system under ER stress. Mol Biol Cell, 24(20):3155-3163.

[134]van den BoomJ, MeyerH, 2018. VCP/p97-mediated unfolding as a principle in protein homeostasis and signaling. Mol Cell, 69(2):182-194.

[135]van der HeijdenJW, OerlemansR, LemsWF, et al., 2009. The proteasome inhibitor bortezomib inhibits the release of NFκB-inducible cytokines and induces apoptosis of activated T cells from rheumatoid arthritis patients. Clin Exp Rheumatol, 27(1):92-98.

[136]van NockerS, SadisS, RubinDM, et al., 1996. The multiubiquitin-chain-binding protein Mcb1 is a component of the 26S proteasome in Saccharomyces cerevisiae and plays a nonessential, substrate-specific role in protein turnover. Mol Cell Biol, 16(11):6020-6028.

[137]VasicV, DenkertN, SchmidtCC, et al., 2020. Hrd1 forms the retrotranslocation pore regulated by auto-ubiquitination and binding of misfolded proteins. Nat Cell Biol, 22(3):274-281.

[138]VijN, FangSY, ZeitlinPL, 2006. Selective inhibition of endoplasmic reticulum-associated degradation rescues ΔF508-cystic fibrosis transmembrane regulator and suppresses interleukin-8 levels: therapeutic implications. J Biol Chem, 281(25):17369-17378.

[139]WalterP, RonD, 2011. The unfolded protein response: from stress pathway to homeostatic regulation. Science, 334(6059):1081-1086.

[140]WangXL, HerrRA, ChuaWJ, et al., 2007. Ubiquitination of serine, threonine, or lysine residues on the cytoplasmic tail can induce ERAD of MHC-I by viral E3 ligase mK3. J Cell Biol, 177(4):613-624.

[141]WangXL, HerrRA, RabelinkM, et al., 2009. Ube2j2 ubiquitinates hydroxylated amino acids on ER-associated degradation substrates. J Cell Biol, 187(5):655-668.

[142]WangY, HuangXY, ZhouJQ, et al., 2012. Trafficking-deficient G572R-hERG and E637K-hERG activate stress and clearance pathways in endoplasmic reticulum. PLoS ONE, 7(1):e29885.

[143]WangY, HaSW, ZhangTP, et al., 2014. Polyubiquitylation of AMF requires cooperation between the gp78 and TRIM25 ubiquitin ligases. Oncotarget, 5(8):2044-2051.

[144]WeiJC, ChenL, LiF, et al., 2018. HRD1-ERAD controls production of the hepatokine FGF21 through CREBH polyubiquitination. EMBO J, 37(22):e98942.

[145]WeiXA, ZhengZY, FengZH, et al., 2022. Sigma-1 receptor attenuates osteoclastogenesis by promoting ER-associated degradation of SERCA2. EMBO Mol Med, 14(7):e15373.

[146]WilkinsonCRM, SeegerM, Hartmann-PetersenR, et al., 2001. Proteins containing the UBA domain are able to bind to multi-ubiquitin chains. Nat Cell Biol, 3(10):939-943.

[147]XiaYX, YanLH, HuangB, et al., 2014. Pathogenic mutation of UBQLN2 impairs its interaction with UBXD8 and disrupts endoplasmic reticulum-associated protein degradation. J Neurochem, 129(1):99-106.

[148]XieY, AvelloM, SchirleM, et al., 2013. Deubiquitinase FAM/USP9X interacts with the E3 ubiquitin ligase SMURF1 protein and protects it from ligase activity-dependent self-degradation. J Biol Chem, 288(5):2976-2985.

[149]XuP, DuongDM, SeyfriedNT, et al., 2009. Quantitative proteomics reveals the function of unconventional ubiquitin chains in proteasomal degradation. Cell, 137(1):133-145.

[150]XuYM, FangDY, 2020. Endoplasmic reticulum-associated degradation and beyond: the multitasking roles for Hrd1 in immune regulation and autoimmunity. J Autoimmun, 109:102423.

[151]XuYM, ZhaoF, QiuQ, et al., 2016. The ER membrane-anchored ubiquitin ligase Hrd1 is a positive regulator of T-cell immunity. Nat Commun, 7:12073.

[152]YagishitaN, OhnedaK, AmanoT, et al., 2005. Essential role of Synoviolin in embryogenesis. J Biol Chem, 280(9):7909-7916.

[153]YamasakiS, YagishitaN, TsuchimochiK, et al., 2005. Rheumatoid arthritis as a hyper-endoplasmic reticulum-associated degradation disease. Arthritis Res Ther, 7(5):181.

[154]YamasakiS, YagishitaN, SasakiT, et al., 2007. Cytoplasmic destruction of p53 by the endoplasmic reticulum-resident ubiquitin ligase ‘Synoviolin’. EMBO J, 26(1):113-122.

[155]YaoTT, CohenRE, 2002. A cryptic protease couples deubiquitination and degradation by the proteasome. Nature, 419(6905):403-407.

[156]YaoX, WuY, XiaoTF, et al., 2022. T-cell-specific Sel1L deletion exacerbates EAE by promoting Th1/Th17-cell differentiation. Mol Immunol, 149:13-26.

[157]YeYH, MeyerHH, RapoportTA, 2001. The AAA ATPase Cdc48/p97 and its partners transport proteins from the ER into the cytosol. Nature, 414(6864):652-656.

[158]YeYH, ShibataY, KikkertM, et al., 2005. Recruitment of the p97 ATPase and ubiquitin ligases to the site of retrotranslocation at the endoplasmic reticulum membrane. Proc Natl Acad Sci USA, 102(40):14132-14138.

[159]YeYL, BaekSH, YeYH, et al., 2018. Proteomic characterization of endogenous substrates of mammalian ubiquitin ligase Hrd1. Cell Biosci, 8:46.

[160]YingZ, WangHF, FanHD, et al., 2009. Gp78, an ER associated E3, promotes SOD1 and ataxin-3 degradation. Hum Mol Genet, 18(22):4268-4281.

[161]YoshidaY, AsahinaM, MurakamiA, et al., 2021. Loss of peptide:N-glycanase causes proteasome dysfunction mediated by a sugar-recognizing ubiquitin ligase. Proc Natl Acad Sci USA, 118(27):e2102902118.

[162]YoungerJM, RenHY, ChenLL, et al., 2004. A foldable CFTRΔF508 biogenic intermediate accumulates upon inhibition of the Hsc70-CHIP E3 ubiquitin ligase. J Cell Biol, 167(6):1075-1085.

[163]ZapunA, DarbyNJ, TessierDC, et al., 1998. Enhanced catalysis of ribonuclease B folding by the interaction of calnexin or calreticulin with ERp57. J Biol Chem, 273(11):6009-6012.

[164]ZhangKY, YangS, WarraichST, et al., 2014. Ubiquilin 2: a component of the ubiquitin-proteasome system with an emerging role in neurodegeneration. Int J Biochem Cell Biol, 50:123-126.

[165]ZhangRZ, PanSX, ZhengSY, et al., 2023. Lipid-anchored proteasomes control membrane protein homeostasis. bioRxiv, prepint.

[166]ZhongXY, ShenYX, BallarP, et al., 2004. AAA ATPase p97/valosin-containing protein interacts with gp78, a ubiquitin ligase for endoplasmic reticulum-associated degradation. J Biol Chem, 279(44):45676-45684.

[167]ZhouZS, TorresM, ShaHB, et al., 2020. Endoplasmic reticulum-associated degradation regulates mitochondrial dynamics in brown adipocytes. Science, 368(6486):54-60.

[168]ZhuB, JiangLL, HuangT, et al., 2017. ER-associated degradation regulates Alzheimer’s amyloid pathology and memory function by modulating γ‍-secretase activity. Nat Commun, 8:1472.

Open peer comments: Debate/Discuss/Question/Opinion

<1>

Please provide your name, email address and a comment





Journal of Zhejiang University-SCIENCE, 38 Zheda Road, Hangzhou 310027, China
Tel: +86-571-87952783; E-mail: cjzhang@zju.edu.cn
Copyright © 2000 - 2024 Journal of Zhejiang University-SCIENCE