• 中国中文核心期刊
  • 中国科学引文数据库核心期刊
  • 中国科技核心期刊
  • 中国高校百佳科技期刊
高级检索

核糖体蛋白的类泛素化修饰及其功能的研究进展

吴玥, 陈依军

吴玥, 陈依军. 核糖体蛋白的类泛素化修饰及其功能的研究进展[J]. 中国药科大学学报, 2022, 53(5): 507-517. DOI: 10.11665/j.issn.1000-5048.20220501
引用本文: 吴玥, 陈依军. 核糖体蛋白的类泛素化修饰及其功能的研究进展[J]. 中国药科大学学报, 2022, 53(5): 507-517. DOI: 10.11665/j.issn.1000-5048.20220501
WU Yue, CHEN Yijun. Recent progress of functional impacts of ubiquitin-like modifications on ribosomal proteins[J]. Journal of China Pharmaceutical University, 2022, 53(5): 507-517. DOI: 10.11665/j.issn.1000-5048.20220501
Citation: WU Yue, CHEN Yijun. Recent progress of functional impacts of ubiquitin-like modifications on ribosomal proteins[J]. Journal of China Pharmaceutical University, 2022, 53(5): 507-517. DOI: 10.11665/j.issn.1000-5048.20220501

核糖体蛋白的类泛素化修饰及其功能的研究进展

基金项目: 国家自然科学基金资助项目(No.81973386)

Recent progress of functional impacts of ubiquitin-like modifications on ribosomal proteins

Funds: This study was supported by the National Natural Science Foundation of China (No.81973386)
  • 摘要: 核糖体蛋白(RP)是核糖体的组成成分,在核糖体生物合成及蛋白翻译过程中发挥重要调控作用。此外,RP在细胞中存在非核糖体功能,并可由多种形式的类泛素化修饰介导实现。RP的类泛素化修饰过程对相应RP的功能和亚细胞定位产生不同的影响,并表现出对多个生理病理过程的调控作用。本文主要对RP的SUMOylation、Neddylation和UFMylation等类泛素化系统进行介绍,并对RP的类泛素化修饰过程及其对细胞增殖、凋亡、自噬和蛋白质生命周期调控方面的影响进行总结,为相关疾病的药物治疗或干预措施带来新的启示。
    Abstract: Ribosomal proteins (RP), components of ribosomes to regulate protein biosynthesis, possess a variety of extra-ribosomal functions which can be mediated by various ubiquitination-like modifications (Ublylation).The Ublylation of RP can result in functional changes and subcellular localizations of corresponding RP, and play regulatory roles on numerous physiological and pathological processes.In this review, in addition to the introduction of Ublylation systems for RP, such as SUMOylation, Neddylation and UFMylation, we summarized recent advances in the elucidation of Ublylation processes for RP and their impacts on cell proliferation, apoptosis, autophagy and protein fate, aiming to lay a foundation for the discovery and development of novel therapeutics based on the intervention of the Ublylation processes for RP.
  • [1] . Annu Rev Biochem,2019,88:281-306.
    [2] de la Cruz J,Gómez-Herreros F,Rodríguez-Galán O,et al. Feedback regulation of ribosome assembly[J]. Curr Genet,2018,64(2):393-404.
    [3] Ramu VS,Dawane A,Lee S,et al. Ribosomal protein QM/RPL10 positively regulates defence and protein translation mechanisms during nonhost disease resistance[J]. Mol Plant Pathol,2020,21(11):1481-1494.
    [4] Johnson AG,Flynn RA,Lapointe CP,et al. A memory of ES25 loss drives resistance phenotypes[J]. Nucleic Acids Res,2020,48(13):7279-7297.
    [5] Li YY,Zhang JT,Sun HL,et al. Lnc-Rps4l-encoded peptide RPS4XL regulates RPS6 phosphorylation and inhibits the proliferation of PASMCs caused by hypoxia[J]. Mol Ther,2021,29(4):1411-1424.
    [6] Jung JH,Lee H,Kim JH,et al. p53-dependent apoptotic effect of puromycin via binding of ribosomal protein L5 and L11 to MDM2 and its combination effect with RITA or doxorubicin[J]. Cancers,2019,11(4):582.
    [7] Ebright RY,Lee S,Wittner BS,et al. Deregulation of ribosomal protein expression and translation promotes breast cancer metastasis[J]. Science,2020,367(6485):1468-1473.
    [8] Park YJ,Kim SH,Kim TS,et al. Ribosomal protein S3 associates with the TFIIH complex and positively regulates nucleotide excision repair[J]. Cell Mol Life Sci,2021,78(7):3591-3606.
    [9] Odintsova TI,Müller EC,Ivanov AV,et al. Characterization and analysis of posttranslational modifications of the human large cytoplasmic ribosomal subunit proteins by mass spectrometry and Edman sequencing[J]. J Protein Chem,2003,22(3):249-258.
    [10] Wirth M,Schick M,Keller U,et al. Ubiquitination and ubiquitin-like modifications in multiple myeloma:biology and therapy[J]. Cancers,2020,12(12):3764.
    [11] Lezzerini M,Penzo M,O′Donohue MF,et al. Ribosomal protein gene RPL9 variants can differentially impair ribosome function and cellular metabolism[J]. Nucleic Acids Res,2019,48(2):770-787.
    [12] Guan JY,Han SC,Wu JE,et al. Ribosomal protein L13 participates in innate immune response induced by foot-and-mouth disease virus[J]. Front Immunol,2021,12:616402.
    [13] Liu PY,Tee AE,Milazzo G,et al. The long noncoding RNA lncNB1 promotes tumorigenesis by interacting with ribosomal protein RPL35[J]. Nat Commun,2019,10:5026.
    [14] Ribezzo F,Snoeren IAM,Ziegler S,et al. Rps14,Csnk1a1 and miRNA145/miRNA146a deficiency cooperate in the clinical phenotype and activation of the innate immune system in the 5q-syndrome[J]. Leukemia,2019,33(7):1759-1772.
    [15] Swatek KN,Komander D. Ubiquitin modifications[J]. Cell Res,2016,26(4):399-422.
    [16] Park J,Cho J,Song EJ. Ubiquitin-proteasome system (UPS) as a target for anticancer treatment[J]. Arch Pharm Res,2020,43(11):1144-1161.
    [17] Dougherty SE,Maduka AO,Inada T,et al. Expanding role of ubiquitin in translational control[J]. Int J Mol Sci,2020,21(3):1151.
    [18] Cappadocia L,Lima CD. Ubiquitin-like protein conjugation:structures,chemistry,and mechanism[J]. Chem Rev,2018,118(3):889-918.
    [19] Oh JG,Watanabe S,Lee A,et al. miR-146a suppresses SUMO1 expression and induces cardiac dysfunction in maladaptive hypertrophy[J]. Circ Res,2018,123(6):673-685.
    [20] Lin H,Yan Y,Luo YF,et al. IP6-assisted CSN-COP1 competition regulates a CRL4-ETV5 proteolytic checkpoint to safeguard glucose-induced insulin secretion[J]. Nat Commun,2021,12:2461.
    [21] Yang JJ,Zhou YL,Xie SD,et al. Metformin induces Ferroptosis by inhibiting UFMylation of SLC7A11 in breast cancer[J]. J Exp Clin Cancer Res,2021,40(1):206.
    [22] Xirodimas DP,Sundqvist A,Nakamura A,et al. Ribosomal proteins are targets for the NEDD8 pathway[J]. EMBO Rep,2008,9(3):280-286.
    [23] Müller S,Ledl A,Schmidt D. SUMO:a regulator of gene expression and genome integrity[J]. Oncogene,2004,23(11):1998-2008.
    [24] Wang LL,Wansleeben C,Zhao SL,et al. SUMO2 is essential while SUMO3 is dispensable for mouse embryonic development[J]. EMBO Rep,2014,15(8):878-885.
    [25] Zhao XL. SUMO-mediated regulation of nuclear functions and signaling processes[J]. Mol Cell,2018,71(3):409-418.
    [26] Bernier-Villamor V,Sampson DA,Matunis MJ,et al. Structural basis for E2-mediated SUMO conjugation revealed by a complex between ubiquitin-conjugating enzyme Ubc9 and RanGAP1[J]. Cell,2002,108(3):345-356.
    [27] Wang TS,Cao Y,Zheng Q,et al. SENP1-Sirt3 signaling controls mitochondrial protein acetylation and metabolism[J]. Mol Cell,2019,75(4):823-834.e5.
    [28] Peng Y,Wang ZX,Wang ZQ,et al. SUMOylation down-regulates rDNA transcription by repressing expression of upstream-binding factor and proto-oncogene c-Myc[J]. J Biol Chem,2019,294(50):19155-19166.
    [29] Schneeweis C,Hassan Z,Schick M,et al. The SUMO pathway in pancreatic cancer:insights and inhibition[J]. Br J Cancer,2021,124(3):531-538.
    [30] Jang CY,Shin HS,Kim HD,et al. Ribosomal protein S3 is stabilized by sumoylation[J]. Biochem Biophys Res Commun,2011,414(3):523-527.
    [31] Kasera M,Ingole KD,Rampuria S,et al. Global sumoylome adjustments in basal defenses of arabidopsis thaliana involve complex interplay between small-ubiquitin like modifiers and the negative immune regulator suppressor of rps4-rld1[J]. Front Cell Dev Biol,2021,9:680760.
    [32] Haindl M,Harasim T,Eick D,et al. The nucleolar SUMO-specific protease SENP3 reverses SUMO modification of nucleophosmin and is required for rRNA processing[J]. EMBO Rep,2008,9(3):273-279.
    [33] Matafora V,D''Amato A,Mori S,et al. Proteomics analysis of nucleolar SUMO-1 target proteins upon proteasome inhibition[J]. Mol Cell Proteom,2009,8(10):2243-2255.
    [34] Enchev RI,Schulman BA,Peter M. Protein neddylation:beyond cullin–RING ligases[J]. Nat Rev Mol Cell Biol,2015,16(1):30-44.
    [35] Li J,Zou JQ,Littlejohn R,et al. Neddylation,an emerging mechanism regulating cardiac development and function[J]. Front Physiol,2020,11:612927.
    [36] Zou T,Zhang JY. Diverse and pivotal roles of neddylation in metabolism and immunity[J]. FEBS J,2021,288(13):3884-3912.
    [37] Song QQ,Feng SQ,Peng WJ,et al. Cullin-RING ligases as promising targets for gastric carcinoma treatment[J]. Pharmacol Res,2021,170:105493.
    [38] Baek K,Scott DC,Schulman BA. NEDD8 and ubiquitin ligation by cullin-RING E3 ligases[J]. Curr Opin Struct Biol,2021,67:101-109.
    [39] Pan ZQ,Kentsis A,Dias DC,et al. Nedd8 on cullin:building an expressway to protein destruction[J]. Oncogene,2004,23(11):1985-1997.
    [40] Li QM,Wang SZ. Advances of relationship between protein Neddylation and cancer[J]. J China Pharm Univ(中国药科大学学报),2018,49(3):272-278.
    [41] Zhang SZ,Sun Y. Cullin RING ligase 5 (CRL-5):neddylation activation and biological functions[J]. Adv Exp Med Biol,2020,1217:261-283.
    [42] Dubiel W,Chaithongyot S,Dubiel D,et al. The COP9 signalosome:a multi-DUB complex[J]. Biomolecules,2020,10(7):1082.
    [43] Liu Y,Deisenroth C,Zhang YP. RP-MDM2-p53 pathway:linking ribosomal biogenesis and tumor surveillance[J]. Trends Cancer,2016,2(4):191-204.
    [44] Xiong XF,Cui DR,Bi YL,et al. Neddylation modification of ribosomal protein RPS27L or RPS27 by MDM2 or NEDP1 regulates cancer cell survival[J]. FASEB J,2020,34(10):13419-13429.
    [45] Sundqvist A,Liu G,Mirsaliotis A,et al. Regulation of nucleolar signalling to p53 through NEDDylation of L11[J]. EMBO Rep,2009,10(10):1132-1139.
    [46] Zhou X,Hao Q,Liao J,et al. Ribosomal protein S14 unties the MDM2–p53 loop upon ribosomal stress[J]. Oncogene,2013,32(3):388-396.
    [47] Zhang J,Bai D,Ma X,et al. hCINAP is a novel regulator of ribosomal protein-HDM2-p53 pathway by controlling NEDDylation of ribosomal protein S14[J]. Oncogene,2014,33(2):246-254.
    [48] Mahata B,Sundqvist A,Xirodimas DP. Recruitment of RPL11 at promoter sites of p53-regulated genes upon nucleolar stress through NEDD8 and in an Mdm2-dependent manner[J]. Oncogene,2012,31(25):3060-3071.
    [49] Yang R,Wang HM,Kang BX,et al. CDK5RAP3,a UFL1 substrate adaptor,is crucial for liver development[J]. Development,2019,146(2):dev169235.
    [50] Banerjee S,Kumar M,Wiener R. Decrypting UFMylation:how proteins are modified with UFM1[J]. Biomolecules,2020,10(10):1442.
    [51] Walczak CP,Leto DE,Zhang LC,et al. Ribosomal protein RPL26 is the principal target of UFMylation[J]. Proc Natl Acad Sci U S A,2019,116(4):1299-1308.
    [52] Kumar M,Padala P,Fahoum J,et al. Structural basis for UFM1 transfer from UBA5 to UFC1[J]. Nat Commun,2021,12:5708.
    [53] Xie Z,Fang Z,Pan ZZ. Ufl1/RCAD,a Ufm1 E3 ligase,has an intricate connection with ER stress[J]. Int J Biol Macromol,2019,135:760-767.
    [54] Wei Y,Xu XZ. UFMylation:a unique & fashionable modification for life[J]. Genom Proteom Bioinform,2016,14(3):140-146.
    [55] Witting KF,Mulder MPC. Highly specialized ubiquitin-like modifications:shedding light into the UFM1 Enigma[J]. Biomolecules,2021,11(2):255.
    [56] Zheng N,Shabek N. Ubiquitin ligases:structure,function,and regulation[J]. Annu Rev Biochem,2017,86:129-157.
    [57] Yoo HM,Kang SH,Kim JY,et al. Modification of ASC1 by UFM1 is crucial for ERα transactivation and breast cancer development[J]. Mol Cell,2014,56(2):261-274.
    [58] Wang LH,Xu Y,Rogers H,et al. UFMylation of RPL26 links translocation-associated quality control to endoplasmic reticulum protein homeostasis[J]. Cell Res,2020,30(1):5-20.
    [59] Simsek D,Tiu GC,Flynn RA,et al. The mammalian ribo-interactome reveals ribosome functional diversity and heterogeneity[J]. Cell,2017,169(6):1051-1065.e18.
    [60] Schuren ABC,Boer IGJ,Bouma EM,et al. The UFM1 pathway impacts HCMV US2-mediated degradation of HLA class I[J]. Molecules,2021,26(2):287.
    [61] van der Veen AG,Ploegh HL. Ubiquitin-like proteins[J]. Annu Rev Biochem,2012,81:323-357.
    [62] Perng YC,Lenschow DJ. ISG15 in antiviral immunity and beyond[J]. Nat Rev Microbiol,2018,16(7):423-439.
    [63] Mustachio LM,Lu Y,Kawakami M,et al. Evidence for the ISG15-specific deubiquitinase USP18 as an antineoplastic target[J]. Cancer Res,2018,78(3):587-592.
    [64] Freitas BT,Scholte FEM,Bergeron é,et al. How ISG15 combats viral infection[J]. Virus Res,2020,286:198036.
    [65] Theng SS,Wang W,Mah WC,et al. Disruption of FAT10-MAD2 binding inhibits tumor progression[J]. Proc Natl Acad Sci U S A,2014,111(49):E5282-E5291.
    [66] Aichem A,Groettrup M. The ubiquitin-like modifier FAT10-much more than a proteasome-targeting signal[J]. J Cell Sci,2020,133(14):jcs246041.
    [67] Lim CB,Zhang DW,Lee CGL. FAT10,a gene up-regulated in various cancers,is cell-cycle regulated[J]. Cell Div,2006,1:20.
    [68] Aichem A,Pelzer C,Lukasiak S,et al. USE1 is a bispecific conjugating enzyme for ubiquitin and FAT10,which FAT10ylates itself in cis[J]. Nat Commun,2010,1:13.
    [69] Aichem A,Catone N,Groettrup M. Investigations into the auto-FAT10ylation of the bispecific E2 conjugating enzyme UBA6-specific E2 enzyme 1[J]. FEBS J,2014,281(7):1848-1859.
    [70] Okumura F,Zou W,Zhang DE. ISG15 modification of the eIF4E cognate 4EHP enhances cap structure-binding activity of 4EHP[J]. Genes Dev,2007,21(3):255-260.
    [71] Spinnenhirn V,Bitzer A,Aichem A,et al. Newly translated proteins are substrates for ubiquitin,ISG15,and FAT10[J]. FEBS Lett,2017,591(1):186-195.
    [72] Nahorski MS,Maddirevula S,Ishimura R,et al. Biallelic UFM1 and UFC1 mutations expand the essential role of UFMylation in brain development[J]. Brain,2018,141(7):1934-1945.
    [73] Su M,Yue ZH,Wang H,et al. UFMylation is activated in vascular remodeling and lipopolysaccharide-induced endothelial cell injury[J]. DNA Cell Biol,2018,37(5):426-431.
    [74] Lin YL,Chung CL,Chen MH,et al. SUMO protease SMT7 modulates ribosomal protein L30 and regulates cell-size checkpoint function[J]. Plant Cell,2020,32(4):1285-1307.
    [75] El Motiam A,Vidal S,de la Cruz-Herrera CF,et al. Interplay between SUMOylation and NEDDylation regulates RPL11 localization and function[J]. FASEB J,2019,33(1):643-651.
    [76] Liang JR,Lingeman E,Luong T,et al. A genome-wide ER-phagy screen highlights key roles of mitochondrial metabolism and ER-resident UFMylation[J]. Cell,2020,180(6):1160-1177.e20.
    [77] Fernández A,Ordó?ez R,Reiter RJ,et al. Melatonin and endoplasmic reticulum stress:relation to autophagy and apoptosis[J]. J Pineal Res,2015,59(3):292-307.
    [78] Bailly A,Perrin A,Bou Malhab LJ,et al. The NEDD8 inhibitor MLN4924 increases the size of the nucleolus and activates p53 through the ribosomal-Mdm2 pathway[J]. Oncogene,2016,35(4):415-426.
    [79] Chang SC,Ding JL. Ubiquitination and SUMOylation in the chronic inflammatory tumor microenvironment[J]. Biochim Biophys Acta Rev Cancer,2018,1870(2):165-175.
    [80] Baek K,Krist DT,Prabu JR,et al. NEDD8 nucleates a multivalent cullin-RING-UBE2D ubiquitin ligation assembly[J]. Nature,2020,578(7795):461-466.
    [81] Liu J,Guan D,Dong MG,et al. UFMylation maintains tumour suppressor p53 stability by antagonizing its ubiquitination[J]. Nat Cell Biol,2020,22(9):1056-1063.
    [82] Wang FT,Zhao B. UBA6 and its bispecific pathways for ubiquitin and FAT10[J]. Int J Mol Sci,2019,20(9):2250.
    [83] Laplaza JM,Bostick M,Scholes DT,et al. Saccharomyces cerevisiae ubiquitin-like protein Rub1 conjugates to cullin proteins Rtt101 and Cul3 in vivo[J]. Biochem J,2004,377(Pt 2):459-467.
    [84] Petroski MD,Deshaies RJ. Function and regulation of cullin-RING ubiquitin ligases[J]. Nat Rev Mol Cell Biol,2005,6(1):9-20.
    [85] Sun XX,Chen YX,Su YL,et al. SUMO protease SENP1 deSUMOylates and stabilizes c-myc[J]. Proc Natl Acad Sci U S A,2018,115(43):10983-10988.
    [86] Han SJ,Shin H,Oh JW,et al. The protein neddylation inhibitor MLN4924 suppresses patient-derived glioblastoma cells via inhibition of ERK and AKT signaling[J]. Cancers,2019,11(12):1849.
    [87] Xie P,Peng ZQ,Chen YJ,et al. Neddylation of PTEN regulates its nuclear import and promotes tumor development[J]. Cell Res,2021,31(3):291-311.
    [88] Sharma P,Kuehn MR. SENP1-modulated sumoylation regulates retinoblastoma protein (RB) and Lamin A/C interaction and stabilization[J]. Oncogene,2016,35(50):6429-6438.
    [89] Barbier-Torres L,Delgado TC,García-Rodríguez JL,et al. Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer[J]. Oncotarget,2015,6(4):2509-2523.
    [90] Lee JS,Chu IS,Heo J,et al. Classification and prediction of survival in hepatocellular carcinoma by gene expression profiling[J]. Hepatology,2004,40(3):667-676.
    [91] Kukkula A,Ojala VK,Mendez LM,et al. Therapeutic potential of targeting the SUMO pathway in cancer[J]. Cancers,2021,13(17):4402.
    [92] Wiechmann S,G?rtner A,Kniss A,et al. Site-specific inhibition of the small ubiquitin-like modifier (SUMO)-conjugating enzyme Ubc9 selectively impairs SUMO chain formation[J]. J Biol Chem,2017,292(37):15340-15351.
    [93] Yu Q,Jiang YH,Sun Y. Anticancer drug discovery by targeting cullin neddylation[J]. Acta Pharm Sin B,2020,10(5):746-765.
    [94] da Silva SR,Paiva SL,Lukkarila JL,et al. Exploring a new frontier in cancer treatment:targeting the ubiquitin and ubiquitin-like activating enzymes[J]. J Med Chem,2013,56(6):2165-2177.
    [95] Zhou LS,Jiang YY,Luo Q,et al. Neddylation:a novel modulator of the tumor microenvironment[J]. Mol Cancer,2019,18(1):77.
    [96] Shi C,Wang Y,Guo YN,et al. Cooperative down-regulation of ribosomal protein L10 and NF-κB signaling pathway is responsible for the anti-proliferative effects by DMAPT in pancreatic cancer cells[J]. Oncotarget,2017,8(21):35009-35018.
    [97] Fan JB,Arimoto KL,Motamedchaboki K,et al. Identification and characterization of a novel ISG15-ubiquitin mixed chain and its role in regulating protein homeostasis[J]. Sci Rep,2015,5:12704.
    [98] Carter SA,Vousden KH. p53-ubl fusions as models of ubiquitination,sumoylation and neddylation of p53[J]. Cell Cycle,2008,7(16):2519-2528.
    [99] El-Asmi F,McManus FP,Brantis-de-Carvalho CE,et al. Cross-talk between SUMOylation and ISGylation in response to interferon[J]. Cytokine,2020,129:155025.
  • 期刊类型引用(2)

    1. 梁莹莹,贾真,付婉婷,卢琳琳. 中药通过影响翻译后修饰过程防治结直肠癌的探讨. 广州中医药大学学报. 2025(02): 505-511 . 百度学术
    2. 陈曦,金亮. 类泛素化修饰在2型糖尿病发生中的研究进展. 中国药科大学学报. 2025(01): 125-131 . 本站查看

    其他类型引用(4)

计量
  • 文章访问数:  1052
  • HTML全文浏览量:  13
  • PDF下载量:  1134
  • 被引次数: 6
出版历程
  • 收稿日期:  2022-02-16
  • 修回日期:  2022-04-06
  • 刊出日期:  2022-10-24

目录

    /

    返回文章
    返回