蛋白质UFM化修饰
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摘要
泛素折叠修饰因子1(ubiquitin-fold modifier 1,UFM1)是类泛素蛋白(ubiquitin-like modifier,UBL)家族的一员,存在于几乎所有的真核细胞中。UFM1对底物的修饰过程与泛素相似,即依次通过UBA5、UFC1和UFL1催化,共价接合在底物的赖氨酸残基上。而UFSP则负责切割UFM1的C端使之成熟,以及去除底物的UFM1修饰。UFM化修饰参与了内质网应激介导的细胞凋亡过程,对其具体作用机制的阐明需要鉴定到UFM1的修饰底物,但目前已经鉴定到UFM1的底物很少。大量研究尚聚焦于UFM修饰酶上。通过对UFM修饰酶和少量修饰底物的研究发现,UFM化修饰参与非酒精性肝病、细胞生成障碍性贫血、髋关节发育不良和神经系统疾病等的发生,以及乳腺癌细胞的增殖与转移和寄生虫的生长发育。本文将对UFM化修饰相关酶和修饰底物进行综述,总结UFM化修饰的生物学功能和在疾病发生发展中的作用。
Ubiquitin-fold modifier 1(UFM1) is a member of the ubiquitin-like modifier(UBL) family and exists in almost all eukaryotic cells. UFM1 shares similar modification processes with ubiquitin. UFM1 is cleaved by UFSP at the C-terminal for maturation and then catalyzed by UBA5, UFC1 and UFL1 successively to finally conjugate to specific lysine residue on the substrates covalently. UFSP is also responsible for deconjugating UFM1 from its substrates. The UFM1 modification is involved in the endoplasmic reticulum(ER) stress-mediated apoptosis, and the explanation to the detailed mechanism of this process requires the identification of UFM1 substrates. However, only a few UFM1 conjugated proteins have been identified so far, and most studies still focused on modification enzymes. It is reported that ufmylation participates in non-alcoholic steatohepatitis, hematopoietic anemia, hip dysplasia, neural system diseases, proliferation and metastasis of breast cancer cells, and the growth and metabolism of parasites. This review summarizes all enzymes and reported substrates of ufmylation, and discusses the biological functions of ufmylation in the development and progression of related diseases.
Ubiquitin-fold modifier 1(UFM1) is a member of the ubiquitin-like modifier(UBL) family and exists in almost all eukaryotic cells. UFM1 shares similar modification processes with ubiquitin. UFM1 is cleaved by UFSP at the C-terminal for maturation and then catalyzed by UBA5, UFC1 and UFL1 successively to finally conjugate to specific lysine residue on the substrates covalently. UFSP is also responsible for deconjugating UFM1 from its substrates. The UFM1 modification is involved in the endoplasmic reticulum(ER) stress-mediated apoptosis, and the explanation to the detailed mechanism of this process requires the identification of UFM1 substrates. However, only a few UFM1 conjugated proteins have been identified so far, and most studies still focused on modification enzymes. It is reported that ufmylation participates in non-alcoholic steatohepatitis, hematopoietic anemia, hip dysplasia, neural system diseases, proliferation and metastasis of breast cancer cells, and the growth and metabolism of parasites. This review summarizes all enzymes and reported substrates of ufmylation, and discusses the biological functions of ufmylation in the development and progression of related diseases.
引文
[1] Daniel J, Liebau E. The ufm1 cascade [J]. Cells, 2014, 3(2): 627-638
[2] Komatsu M, Chiba T, Tatsumi K, et al. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier [J]. EMBO J, 2004, 23(9): 1977-1986
[3] 沈琼娜, 胡小磊, 陈凤玲. 泛素折叠修饰因子1作用的研究进展[J]. 医学综述(Shen QN, Hu XL, Chen FL. Research advance in the effect of ubiquitin fold modifier 1 [J]. Med Recapitulate), 2014, 20(19): 3501-3503
[4] Wei Y, Xu X. UFMylation: A unique & fashionable modification for life [J]. Genomics Proteomics Bioinformatics, 2016, 14(3): 140-146
[5] Kang SH, Kim GR, Seong M, et al. Two novel ubiquitin-fold modifier 1 (Ufm1)-specific proteases, UfSP1 and UfSP2 [J]. J Biol Chem, 2007, 282(8): 5256-5262
[6] Grau-Bove X, Sebe-Pedros A, Ruiz-Trillo I. The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin [J]. Mol Biol Evol, 2015, 32(3): 726-739
[7] Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue-based map of the human proteome [J]. Science, 2015, 347(6220): 1260419
[8] Zheng M, Gu X, Zheng D, et al. UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins [J]. J Cell Biochem, 2008, 104(6): 2324-2334
[9] Schulman BA, Harper JW. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways [J]. Nat Rev Mol Cell Biol, 2009, 10(5): 319-331
[10] Bacik JP, Walker JR, Ali M, et al. Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme [J]. J Biol Chem, 2010, 285(26): 20273-20280
[11] Xie S. Characterization, crystallization and preliminary X-ray crystallographic analysis of the Uba5 fragment necessary for high-efficiency activation of Ufm1 [J]. Acta Crystallogr F Struct Biol Commun, 2014, 70(Pt 6): 765-768
[12] Mashahreh B, Hassouna F, Soudah N, et al. Trans-binding of UFM1 to UBA5 stimulates UBA5 homodimerization and ATP binding [J]. FASEB J, 2018, 32(5): 2794-2802
[13] Oweis W, Padala P, Hassouna F, et al. Trans-binding mechanism of ubiquitin-like protein activation revealed by a UBA5-UFM1 complex [J]. Cell Rep, 2016, 16(12): 3113-3120
[14] Liu G, Forouhar F, Eletsky A, et al. NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1- UBA5-UFC1 ubiquination pathway [J]. J Struct Funct Genomics, 2009, 10(2): 127-136
[15] Mizushima T, Tatsumi K, Ozaki Y, et al. Crystal structure of Ufc1, the Ufm1-conjugating enzyme [J]. Biochem Biophys Res Commun, 2007, 362(4): 1079-1084
[16] Tatsumi K, Sou YS, Tada N, et al. A novel type of E3 ligase for the Ufm1 conjugation system [J]. J Biol Chem, 2010, 285(8): 5417-5427
[17] Wu J, Lei G, Mei M, et al. A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB signaling [J]. J Biol Chem, 2010, 285(20): 15126-15136
[18] Cai Y, Pi W, Sivaprakasam S, et al. UFBP1, a key component of the Ufm1 conjugation system, is essential for ufmylation-mediated regulation of erythroid development [J]. PLoS Genet, 2015, 11(11): e1005643
[19] Xu J, Wu RC, O'Malley BW. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family [J]. Nat Rev Cancer, 2009, 9(9): 615-630
[20] Roberts AM, Miyamoto DK, Huffman TR, et al. Chemoproteomic screening of covalent ligands reveals UBA5 as a novel pancreatic cancer target [J]. ACS Chem Biol, 2017, 12(4): 899-904
[21] Kim HJ, Yi JY, Sung HS, et al. Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation [J]. Mol Cell Biol, 1999, 19(9): 6323-6332
[22] Xi P, Ding D, Zhou J, et al. DDRGK1 regulates NF-kappaB activity by modulating IkappaBalpha stability [J]. PLoS One, 2013, 8(5): e64231
[23] Kwon J, Cho HJ, Han SH, et al. A novel LZAP-binding protein, NLBP, inhibits cell invasion [J]. J Biol Chem, 2010, 285(16): 12232-12240
[24] Shiwaku H, Yoshimura N, Tamura T, et al. Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity [J]. EMBO J, 2010, 29(14): 2446-2460
[25] Hu X, Pang Q, Shen Q, et al. Ubiquitin-fold modifier 1 inhibits apoptosis by suppressing the endoplasmic reticulum stress response in Raw264.7 cells [J]. Int J Mol Med, 2014, 33(6): 1539-1546
[26] Zhang Y, Zhang M, Wu J, et al. Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking [J]. PLoS One, 2012, 7(11): e48587
[27] Zhang M, Zhu X, Zhang Y, et al. RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis [J]. Cell Death Differ, 2015, 22(12): 1922-1934
[28] Hertel P, Daniel J, Stegehake D, et al. The ubiquitin-fold modifier 1 (Ufm1) cascade of Caenorhabditis elegans [J]. J Biol Chem, 2013, 288(15): 10661-10671
[29] Ha BH, Jeon YJ, Shin SC, et al. Structure of ubiquitin-fold modifier 1-specific protease UfSP2 [J]. J Biol Chem, 2011, 286(12): 10248-10257
[30] Dudek, Michal. Investigations of the Ufm1 pathway and its association with a familial form of hip dysplasia [D]. University of Manchester, 2013
[31] Lu H, Yang Y, Allister EM, et al. The identification of potential factors associated with the development of type 2 diabetes: a quantitative proteomics approach [J]. Mol Cell Proteomics, 2008, 7(8): 1434-1451
[32] Cai Y, Singh N, Li H. Essential role of Ufm1 conjugation in the hematopoietic system [J]. Exp Hematol, 2016, 44(6): 442-446
[33] Azfer A, Niu J, Rogers LM, et al. Activation of endoplasmic reticulum stress response during the development of ischemic heart disease [J]. Am J Physiol Heart Circ Physiol, 2006, 291(3): H1411-1420
[34] Lemaire K, Moura RF, Granvik M, et al. Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis [J]. PLoS One, 2011, 6(4): e18517
[35] Tatsumi K, Yamamoto-Mukai H, Shimizu R, et al. The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice [J]. Nat Commun, 2011, 2: 181
[36] Miller C, Cai Y, Patton T, et al. RCAD/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas [J]. Am J Physiol Gastrointest Liver Physiol, 2017, 312(3): G314-G326
[37] Cilliers HJ, Beighton P. Beukes familial hip dysplasia: an autosomal dominant entity [J]. Am J Med Genet, 1990, 36(4): 386-390
[38] Roby P, Eyre S, Worthington J, et al. Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint maps to an 11-cM region on chromosome 4q35 [J]. Am J Hum Genet, 1999, 64(3): 904-908
[39] Watson CM, Crinnion LA, Gleghorn L, et al. Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase 2 gene, UFSP2, in an extended South African family with Beukes hip dysplasia [J]. S Afr Med J, 2015, 105(7): 558-563
[40] Di Rocco M, Rusmini M, Caroli F, et al. Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation [J]. Clin Genet, 2018, 93(3): 671-674
[41] Yoo HM, Kang SH, Kim JY, et al. Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development [J]. Mol Cell, 2014, 56(2): 261-274
[42] Zhu Y, Lei Q, Li D, et al. Proteomic and biochemical analyses reveal a novel mechanism for promoting protein ubiquitination and degradation by UFBP1, a key component of ufmylation [J]. J Proteome Res, 2018, 17(4): 1509-1520
[43] Zou M, Wang J, Gao J, et al. Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells [J]. Oncol Lett, 2018, 15(3): 2889-2898
[44] Gannavaram S, Connelly PS, Daniels MP, et al. Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of beta-oxidation of fatty acids and blocks cell division in the amastigote stage [J]. Mol Microbiol, 2012, 86(1): 187-198
[45] Gannavaram S, Sharma P, Duncan RC, et al. Mitochondrial associated ubiquitin fold modifier-1 mediated protein conjugation in Leishmania donovani [J]. PLoS One, 2011, 6(1): e16156
[46] Gannavaram S, Davey S, Lakhal-Naouar I, et al. Deletion of ubiquitin fold modifier protein Ufm1 processing peptidase Ufsp in L. donovani abolishes Ufm1 processing and alters pathogenesis [J]. PLoS Negl Trop Dis, 2014, 8(2): e2707
[47] Colin E, Daniel J, Ziegler A, et al. Biallelic variants in UBA5 reveal that disruption of the UFM1 cascade can result in early-onset encephalopathy [J]. Am J Hum Genet, 2016, 99(3): 695-703
[48] Duan R, Shi Y, Yu L, et al. UBA5 mutations cause a new form of autosomal recessive cerebellar ataxia [J]. PLoS One, 2016, 11(2): e0149039
[49] 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
[50] Hamilton EMC, Bertini E, Kalaydjieva L, et al. UFM1 founder mutation in the Roma population causes recessive variant of H-ABC [J]. Neurology, 2017, 89(17): 1821-1828
[51] Mignon-Ravix C, Milh M, Kaiser CS, et al. Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst [J]. Hum Mutat, 2018, 39(7): 934-938
[52] Lee YJ, Johnson KR, Hallenbeck JM. Global protein conjugation by ubiquitin-like-modifiers during ischemic stress is regulated by microRNAs and confers robust tolerance to ischemia [J]. PLoS One, 2012, 7(10): e47787
[53] Liu H, Gong M, French BA, et al. Mallory-Denk Body (MDB) formation modulates Ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) [J]. Exp Mol Pathol, 2014, 97(3): 477-483
[54] Liu H, Li J, Tillman B, et al. Ufmylation and FATylation pathways are downregulated in human alcoholic and nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs) form [J]. Exp Mol Pathol, 2014, 97(1): 81-88
[55] Tu J, Chen Y, Cai L, et al. Functional proteomics study reveals SUMOylation of TFⅡ-Ⅰ is involved in liver cancer cell proliferation[J]. J Proteome Res, 2015, 14(6): 2385-2397
[56] Cai L, Tu J, Song L, et al. Proteome-wide mapping of endogenous SOMOylation sites in mouse testis[J].Mol Cell Proteomics, 2017, 16(5): 717-727.
[2] Komatsu M, Chiba T, Tatsumi K, et al. A novel protein-conjugating system for Ufm1, a ubiquitin-fold modifier [J]. EMBO J, 2004, 23(9): 1977-1986
[3] 沈琼娜, 胡小磊, 陈凤玲. 泛素折叠修饰因子1作用的研究进展[J]. 医学综述(Shen QN, Hu XL, Chen FL. Research advance in the effect of ubiquitin fold modifier 1 [J]. Med Recapitulate), 2014, 20(19): 3501-3503
[4] Wei Y, Xu X. UFMylation: A unique & fashionable modification for life [J]. Genomics Proteomics Bioinformatics, 2016, 14(3): 140-146
[5] Kang SH, Kim GR, Seong M, et al. Two novel ubiquitin-fold modifier 1 (Ufm1)-specific proteases, UfSP1 and UfSP2 [J]. J Biol Chem, 2007, 282(8): 5256-5262
[6] Grau-Bove X, Sebe-Pedros A, Ruiz-Trillo I. The eukaryotic ancestor had a complex ubiquitin signaling system of archaeal origin [J]. Mol Biol Evol, 2015, 32(3): 726-739
[7] Uhlen M, Fagerberg L, Hallstrom BM, et al. Proteomics. Tissue-based map of the human proteome [J]. Science, 2015, 347(6220): 1260419
[8] Zheng M, Gu X, Zheng D, et al. UBE1DC1, an ubiquitin-activating enzyme, activates two different ubiquitin-like proteins [J]. J Cell Biochem, 2008, 104(6): 2324-2334
[9] Schulman BA, Harper JW. Ubiquitin-like protein activation by E1 enzymes: the apex for downstream signalling pathways [J]. Nat Rev Mol Cell Biol, 2009, 10(5): 319-331
[10] Bacik JP, Walker JR, Ali M, et al. Crystal structure of the human ubiquitin-activating enzyme 5 (UBA5) bound to ATP: mechanistic insights into a minimalistic E1 enzyme [J]. J Biol Chem, 2010, 285(26): 20273-20280
[11] Xie S. Characterization, crystallization and preliminary X-ray crystallographic analysis of the Uba5 fragment necessary for high-efficiency activation of Ufm1 [J]. Acta Crystallogr F Struct Biol Commun, 2014, 70(Pt 6): 765-768
[12] Mashahreh B, Hassouna F, Soudah N, et al. Trans-binding of UFM1 to UBA5 stimulates UBA5 homodimerization and ATP binding [J]. FASEB J, 2018, 32(5): 2794-2802
[13] Oweis W, Padala P, Hassouna F, et al. Trans-binding mechanism of ubiquitin-like protein activation revealed by a UBA5-UFM1 complex [J]. Cell Rep, 2016, 16(12): 3113-3120
[14] Liu G, Forouhar F, Eletsky A, et al. NMR and X-RAY structures of human E2-like ubiquitin-fold modifier conjugating enzyme 1 (UFC1) reveal structural and functional conservation in the metazoan UFM1- UBA5-UFC1 ubiquination pathway [J]. J Struct Funct Genomics, 2009, 10(2): 127-136
[15] Mizushima T, Tatsumi K, Ozaki Y, et al. Crystal structure of Ufc1, the Ufm1-conjugating enzyme [J]. Biochem Biophys Res Commun, 2007, 362(4): 1079-1084
[16] Tatsumi K, Sou YS, Tada N, et al. A novel type of E3 ligase for the Ufm1 conjugation system [J]. J Biol Chem, 2010, 285(8): 5417-5427
[17] Wu J, Lei G, Mei M, et al. A novel C53/LZAP-interacting protein regulates stability of C53/LZAP and DDRGK domain-containing Protein 1 (DDRGK1) and modulates NF-kappaB signaling [J]. J Biol Chem, 2010, 285(20): 15126-15136
[18] Cai Y, Pi W, Sivaprakasam S, et al. UFBP1, a key component of the Ufm1 conjugation system, is essential for ufmylation-mediated regulation of erythroid development [J]. PLoS Genet, 2015, 11(11): e1005643
[19] Xu J, Wu RC, O'Malley BW. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family [J]. Nat Rev Cancer, 2009, 9(9): 615-630
[20] Roberts AM, Miyamoto DK, Huffman TR, et al. Chemoproteomic screening of covalent ligands reveals UBA5 as a novel pancreatic cancer target [J]. ACS Chem Biol, 2017, 12(4): 899-904
[21] Kim HJ, Yi JY, Sung HS, et al. Activating signal cointegrator 1, a novel transcription coactivator of nuclear receptors, and its cytosolic localization under conditions of serum deprivation [J]. Mol Cell Biol, 1999, 19(9): 6323-6332
[22] Xi P, Ding D, Zhou J, et al. DDRGK1 regulates NF-kappaB activity by modulating IkappaBalpha stability [J]. PLoS One, 2013, 8(5): e64231
[23] Kwon J, Cho HJ, Han SH, et al. A novel LZAP-binding protein, NLBP, inhibits cell invasion [J]. J Biol Chem, 2010, 285(16): 12232-12240
[24] Shiwaku H, Yoshimura N, Tamura T, et al. Suppression of the novel ER protein Maxer by mutant ataxin-1 in Bergman glia contributes to non-cell-autonomous toxicity [J]. EMBO J, 2010, 29(14): 2446-2460
[25] Hu X, Pang Q, Shen Q, et al. Ubiquitin-fold modifier 1 inhibits apoptosis by suppressing the endoplasmic reticulum stress response in Raw264.7 cells [J]. Int J Mol Med, 2014, 33(6): 1539-1546
[26] Zhang Y, Zhang M, Wu J, et al. Transcriptional regulation of the Ufm1 conjugation system in response to disturbance of the endoplasmic reticulum homeostasis and inhibition of vesicle trafficking [J]. PLoS One, 2012, 7(11): e48587
[27] Zhang M, Zhu X, Zhang Y, et al. RCAD/Ufl1, a Ufm1 E3 ligase, is essential for hematopoietic stem cell function and murine hematopoiesis [J]. Cell Death Differ, 2015, 22(12): 1922-1934
[28] Hertel P, Daniel J, Stegehake D, et al. The ubiquitin-fold modifier 1 (Ufm1) cascade of Caenorhabditis elegans [J]. J Biol Chem, 2013, 288(15): 10661-10671
[29] Ha BH, Jeon YJ, Shin SC, et al. Structure of ubiquitin-fold modifier 1-specific protease UfSP2 [J]. J Biol Chem, 2011, 286(12): 10248-10257
[30] Dudek, Michal. Investigations of the Ufm1 pathway and its association with a familial form of hip dysplasia [D]. University of Manchester, 2013
[31] Lu H, Yang Y, Allister EM, et al. The identification of potential factors associated with the development of type 2 diabetes: a quantitative proteomics approach [J]. Mol Cell Proteomics, 2008, 7(8): 1434-1451
[32] Cai Y, Singh N, Li H. Essential role of Ufm1 conjugation in the hematopoietic system [J]. Exp Hematol, 2016, 44(6): 442-446
[33] Azfer A, Niu J, Rogers LM, et al. Activation of endoplasmic reticulum stress response during the development of ischemic heart disease [J]. Am J Physiol Heart Circ Physiol, 2006, 291(3): H1411-1420
[34] Lemaire K, Moura RF, Granvik M, et al. Ubiquitin fold modifier 1 (UFM1) and its target UFBP1 protect pancreatic beta cells from ER stress-induced apoptosis [J]. PLoS One, 2011, 6(4): e18517
[35] Tatsumi K, Yamamoto-Mukai H, Shimizu R, et al. The Ufm1-activating enzyme Uba5 is indispensable for erythroid differentiation in mice [J]. Nat Commun, 2011, 2: 181
[36] Miller C, Cai Y, Patton T, et al. RCAD/BiP pathway is necessary for the proper synthesis of digestive enzymes and secretory function of the exocrine pancreas [J]. Am J Physiol Gastrointest Liver Physiol, 2017, 312(3): G314-G326
[37] Cilliers HJ, Beighton P. Beukes familial hip dysplasia: an autosomal dominant entity [J]. Am J Med Genet, 1990, 36(4): 386-390
[38] Roby P, Eyre S, Worthington J, et al. Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint maps to an 11-cM region on chromosome 4q35 [J]. Am J Hum Genet, 1999, 64(3): 904-908
[39] Watson CM, Crinnion LA, Gleghorn L, et al. Identification of a mutation in the ubiquitin-fold modifier 1-specific peptidase 2 gene, UFSP2, in an extended South African family with Beukes hip dysplasia [J]. S Afr Med J, 2015, 105(7): 558-563
[40] Di Rocco M, Rusmini M, Caroli F, et al. Novel spondyloepimetaphyseal dysplasia due to UFSP2 gene mutation [J]. Clin Genet, 2018, 93(3): 671-674
[41] Yoo HM, Kang SH, Kim JY, et al. Modification of ASC1 by UFM1 is crucial for ERalpha transactivation and breast cancer development [J]. Mol Cell, 2014, 56(2): 261-274
[42] Zhu Y, Lei Q, Li D, et al. Proteomic and biochemical analyses reveal a novel mechanism for promoting protein ubiquitination and degradation by UFBP1, a key component of ufmylation [J]. J Proteome Res, 2018, 17(4): 1509-1520
[43] Zou M, Wang J, Gao J, et al. Phosphoproteomic analysis of the antitumor effects of ginsenoside Rg3 in human breast cancer cells [J]. Oncol Lett, 2018, 15(3): 2889-2898
[44] Gannavaram S, Connelly PS, Daniels MP, et al. Deletion of mitochondrial associated ubiquitin fold modifier protein Ufm1 in Leishmania donovani results in loss of beta-oxidation of fatty acids and blocks cell division in the amastigote stage [J]. Mol Microbiol, 2012, 86(1): 187-198
[45] Gannavaram S, Sharma P, Duncan RC, et al. Mitochondrial associated ubiquitin fold modifier-1 mediated protein conjugation in Leishmania donovani [J]. PLoS One, 2011, 6(1): e16156
[46] Gannavaram S, Davey S, Lakhal-Naouar I, et al. Deletion of ubiquitin fold modifier protein Ufm1 processing peptidase Ufsp in L. donovani abolishes Ufm1 processing and alters pathogenesis [J]. PLoS Negl Trop Dis, 2014, 8(2): e2707
[47] Colin E, Daniel J, Ziegler A, et al. Biallelic variants in UBA5 reveal that disruption of the UFM1 cascade can result in early-onset encephalopathy [J]. Am J Hum Genet, 2016, 99(3): 695-703
[48] Duan R, Shi Y, Yu L, et al. UBA5 mutations cause a new form of autosomal recessive cerebellar ataxia [J]. PLoS One, 2016, 11(2): e0149039
[49] 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
[50] Hamilton EMC, Bertini E, Kalaydjieva L, et al. UFM1 founder mutation in the Roma population causes recessive variant of H-ABC [J]. Neurology, 2017, 89(17): 1821-1828
[51] Mignon-Ravix C, Milh M, Kaiser CS, et al. Abnormal function of the UBA5 protein in a case of early developmental and epileptic encephalopathy with suppression-burst [J]. Hum Mutat, 2018, 39(7): 934-938
[52] Lee YJ, Johnson KR, Hallenbeck JM. Global protein conjugation by ubiquitin-like-modifiers during ischemic stress is regulated by microRNAs and confers robust tolerance to ischemia [J]. PLoS One, 2012, 7(10): e47787
[53] Liu H, Gong M, French BA, et al. Mallory-Denk Body (MDB) formation modulates Ufmylation expression epigenetically in alcoholic hepatitis (AH) and non-alcoholic steatohepatitis (NASH) [J]. Exp Mol Pathol, 2014, 97(3): 477-483
[54] Liu H, Li J, Tillman B, et al. Ufmylation and FATylation pathways are downregulated in human alcoholic and nonalcoholic steatohepatitis, and mice fed DDC, where Mallory-Denk bodies (MDBs) form [J]. Exp Mol Pathol, 2014, 97(1): 81-88
[55] Tu J, Chen Y, Cai L, et al. Functional proteomics study reveals SUMOylation of TFⅡ-Ⅰ is involved in liver cancer cell proliferation[J]. J Proteome Res, 2015, 14(6): 2385-2397
[56] Cai L, Tu J, Song L, et al. Proteome-wide mapping of endogenous SOMOylation sites in mouse testis[J].Mol Cell Proteomics, 2017, 16(5): 717-727.