线性泛素化修饰在肿瘤发生发展中的研究进展
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摘要
泛素化修饰在许多生理过程中起着重要作用,如细胞存活、细胞分化以及免疫反应等。线性泛素化修饰是近年来发现的一种特殊类型的翻译后修饰方式。该过程主要是由泛素连接酶复合体LUBAC催化和特异性去泛素化酶水解完成,目前的研究主要涉及免疫、炎症反应和血管生成等过程。随着研究的进展,发现线性泛素化修饰在肿瘤的发生过程中也具有重要的作用。文章将从LUBAC复合体、线性去泛素化酶、线性泛素化修饰的底物以及相关的小分子抑制剂等方面进行综述。
Ubiquitination plays an important role in many physiological processes,such as cell survival,cell differentiation,and immune response. Linear ubiquitination is a unique type of post-translational modification found in recent years. The process is mainly carried out by the ubiquitin ligase complex LUBAC catalysis and specific deubiquitination enzyme hydrolysis. The current research mainly involves in immunity,inflammation and angiogenesis. With the development of research,it has been found that linear ubiquitination also plays an important role in tumorigenesis. This article reviews the LUBAC complex,linear deubiquitinating enzymes,substrates of linear ubiquitination and related small molecule inhibitors.
Ubiquitination plays an important role in many physiological processes,such as cell survival,cell differentiation,and immune response. Linear ubiquitination is a unique type of post-translational modification found in recent years. The process is mainly carried out by the ubiquitin ligase complex LUBAC catalysis and specific deubiquitination enzyme hydrolysis. The current research mainly involves in immunity,inflammation and angiogenesis. With the development of research,it has been found that linear ubiquitination also plays an important role in tumorigenesis. This article reviews the LUBAC complex,linear deubiquitinating enzymes,substrates of linear ubiquitination and related small molecule inhibitors.
引文
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[19] Zhu J,Zhao C,Zhuang T,et al. RING finger protein 31 promotes p53 degradation in breast cancer cells[J]. Oncogene,2016,35(15):1955-1964.
[20] Zhu J,Zhuang T,Yang H,et al. Atypical ubiquitin ligase RNF31:the nuclear factor modulator in breast cancer progression[J]. BMC Cancer,2016,16:538.
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[22] Lafont E,Kantari-Mimoun C,Draber P,et al. The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death[J]. EMBO J,2017,36(9):1147-1166.
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[26] Wei R,Xu LW,Liu J,et al. SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination[J]. Genes Dev,2017,31(11):1162-1176.
[27] Shimizu Y,Peltzer N,Sevko A,et al. The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis[J]. Hepatology,2017,65(6):1963-1978.
[28] Huang H,Du T,Zhang Y,et al. Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals[J]. Prostate,2017,77(7):718-728.
[29] Tamiya H,Kim H,Klymenko O,et al. SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth[J]. J Clin Invest,2018,128(1):517-530.
[30] Queisser MA,Dada LA,Deiss-Yehiely N,et al. HOIL-1L functions as the PKCzeta ubiquitin ligase to promote lung tumor growth[J]. Am J Respir Crit Care Med,2014,190(6):688-698.
[31] Tomonaga M,Hashimoto N,Tokunaga F,et al. Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells[J]. Int J Oncol,2012,40(2):409-417.
[32] Elton L,Carpentier I,Staal J,et al. MALT1 cleaves the E3ubiquitin ligase HOIL-1 in activated T cells,generating a dominant negative inhibitor of LUBAC-induced NF-kappaB signaling[J]. FEBS J,2016,283(3):403-412.
[33] Fontan L,Yang C,Kabaleeswaran V,et al. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo[J]. Cancer Cell,2012,22(6):812-824.
[34] Liang Y,Seymour RE,Sundberg JP. Inhibition of NF-kappaB signaling retards eosinophilic dermatitis in SHARPIN-deficient mice[J]. J Invest Dermatol,2011,131(1):141-149.
[35] Rivkin E,Almeida SM,Ceccarelli DF,et al. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis[J]. Nature,2013,498(7454):318-324.
[36] Heger K,Wickliffe KE,Ndoja A,et al. OTULIN limits cell death and inflammation by deubiquitinating LUBAC[J]. Nature,2018,559(7712):120-124
[37] Damgaard RB,Walker JA,Marco-Casanova P,et al. The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity[J]. Cell,2016,166(5):1215-1230.e1220.
[38] Fiil BK,Damgaard RB,Wagner SA,et al. OTULIN restricts Met1-linked ubiquitination to control innate immune signaling[J]. Mol Cell,2013,50(6):818-830.
[39] Yang Y,Schmitz R,Mitala J,et al. Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms[J]. Cancer Discov,2014,4(4):480-493.
[40] Grumati P,Dikic I. Germline polymorphisms in RNF31 regulate linear ubiquitination and oncogenic signaling[J]. Cancer Discov,2014,4(4):394-396.
[41] Yang YK,Yang C,Chan W,et al. Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10(Bcl10)during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11(CARD11)Signaling[J]. J Biol Chem,2016,291(50):25921-25936.
[42] Rodgers MA,Bowman JW,Fujita H,et al. The linear ubiquitin assembly complex(LUBAC)is essential for NLRP3 inflammasome activation[J]. J Exp Med,2014,211(7):1333-1347.
[43] Qin Z,Jiang W,Wang G,et al. Linear ubiquitin chain induces apoptosis and inhibits tumor growth[J]. Apoptosis,2017,23(1):16-26.
[2] Grabbe C,Husnjak K,Dikic I. The spatial and temporal organization of ubiquitin networks[J]. Nat Rev Mol Cell Biol,2011,12(5):295-307.
[3]王少冰,王芳.泛素结合酶E2C与肿瘤的关系研究进展[J].医学研究生学报,2015,28(5):543-548.
[4] Pickart CM,Fushman D. Polyubiquitin chains:polymeric protein signals[J]. Curr Opin Chem Biol,2004,8(6):610-616.
[5] Pickart CM. Back to the future with ubiquitin[J]. Cell,2004,116(2):181-190.
[6] Popovic D,Vucic D,Dikic I. Ubiquitination in disease pathogenesis and treatment[J]. Nat Med,2014,20(11):1242-1253.
[7] Swatek KN,Komander D. Ubiquitin modifications[J]. Cell Res,2016,26(4):399-422.
[8] Bremm A,Komander D. Emerging roles for Lys11-linked polyubiquitin in cellular regulation[J]. Trends Biochem Sci,2011,36(7):355-363.
[9] Kirisako T,Kamei K,Murata S,et al. A ubiquitin ligase complex assembles linear polyubiquitin chains[J]. EMBO J,2006,25(20):4877-4887.
[10] Ikeda F,Deribe YL,Skanland SS,et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis[J]. Nature,2011,471(7340):637-641.
[11] Fujita H,Tokunaga A,Shimizu S,et al. Cooperative Domain Formation by Homologous Motifs in HOIL-1L and SHARPIN Plays A Crucial Role in LUBAC Stabilization[J]. Cell Rep,2018,23(4):1192-1204.
[12] Sasaki K,Iwai K. Roles of linear ubiquitinylation,a crucial regulator of NF-kappaB and cell death,in the immune system[J].Immunol Rev,2015,266(1):175-189.
[13] Iwai K,Fujita H,Sasaki Y. Linear ubiquitin chains:NF-kappaB signalling,cell death and beyond[J]. Nat Rev Mol Cell Biol,2014,15(8):503-508.
[14] Elliott PR,Nielsen SV,Marco-Casanova P,et al. Molecular basis and regulation of OTULIN-LUBAC interaction[J]. Mol Cell,2014,54(3):335-348.
[15] Schaeffer V,Akutsu M,Olma MH,et al. Binding of OTULIN to the PUB domain of HOIP controls NF-kappaB signaling[J].Mol Cell,2014,54(3):349-361.
[16] Keusekotten K,Elliott PR,Glockner L,et al. OTULIN antagonizes LUBAC signaling by specifically hydrolyzing Met1-linked polyubiquitin[J]. Cell,2013,153(6):1312-1326.
[17] Thompson HG,Harris JW,Lin L,et al. Identification of the protein Zibra,its genomic organization,regulation,and expression in breast cancer cells[J]. Exp Cell Res,2004,295(2):448-459.
[18] Zhu J,Zhao C,Kharman-Biz A,et al. The atypical ubiquitin ligase RNF31 stabilizes estrogen receptorαand modulates estrogen-stimulated breast cancer cell proliferation[J]. Oncogene,2014,33(34):4340-4351.
[19] Zhu J,Zhao C,Zhuang T,et al. RING finger protein 31 promotes p53 degradation in breast cancer cells[J]. Oncogene,2016,35(15):1955-1964.
[20] Zhu J,Zhuang T,Yang H,et al. Atypical ubiquitin ligase RNF31:the nuclear factor modulator in breast cancer progression[J]. BMC Cancer,2016,16:538.
[21] Tokunaga F,Sakata S,Saeki Y,et al. Involvement of linear polyubiquitylation of NEMO in NF-kappaB activation[J]. Nat Cell Biol,2009,11(2):123-132.
[22] Lafont E,Kantari-Mimoun C,Draber P,et al. The linear ubiquitin chain assembly complex regulates TRAIL-induced gene activation and cell death[J]. EMBO J,2017,36(9):1147-1166.
[23] Ben-Neriah Y,Karin M. Inflammation meets cancer,with NFkappaB as the matchmaker[J]. Nat Immunol,2011,12(8):715-723.
[24] Karin M. Nuclear factor-kappaB in cancer development and progression[J]. Nature,2006,441(7092):431-436.
[25] MacKay C,Carroll E,Ibrahim AFM,et al. E3 ubiquitin ligase HOIP attenuates apoptotic cell death induced by cisplatin[J].Cancer Res,2014,74(8):2246-2257.
[26] Wei R,Xu LW,Liu J,et al. SPATA2 regulates the activation of RIPK1 by modulating linear ubiquitination[J]. Genes Dev,2017,31(11):1162-1176.
[27] Shimizu Y,Peltzer N,Sevko A,et al. The Linear ubiquitin chain assembly complex acts as a liver tumor suppressor and inhibits hepatocyte apoptosis and hepatitis[J]. Hepatology,2017,65(6):1963-1978.
[28] Huang H,Du T,Zhang Y,et al. Elevation of SHARPIN Protein Levels in Prostate Adenocarcinomas Promotes Metastasis and Impairs Patient Survivals[J]. Prostate,2017,77(7):718-728.
[29] Tamiya H,Kim H,Klymenko O,et al. SHARPIN-mediated regulation of protein arginine methyltransferase 5 controls melanoma growth[J]. J Clin Invest,2018,128(1):517-530.
[30] Queisser MA,Dada LA,Deiss-Yehiely N,et al. HOIL-1L functions as the PKCzeta ubiquitin ligase to promote lung tumor growth[J]. Am J Respir Crit Care Med,2014,190(6):688-698.
[31] Tomonaga M,Hashimoto N,Tokunaga F,et al. Activation of nuclear factor-kappa B by linear ubiquitin chain assembly complex contributes to lung metastasis of osteosarcoma cells[J]. Int J Oncol,2012,40(2):409-417.
[32] Elton L,Carpentier I,Staal J,et al. MALT1 cleaves the E3ubiquitin ligase HOIL-1 in activated T cells,generating a dominant negative inhibitor of LUBAC-induced NF-kappaB signaling[J]. FEBS J,2016,283(3):403-412.
[33] Fontan L,Yang C,Kabaleeswaran V,et al. MALT1 small molecule inhibitors specifically suppress ABC-DLBCL in vitro and in vivo[J]. Cancer Cell,2012,22(6):812-824.
[34] Liang Y,Seymour RE,Sundberg JP. Inhibition of NF-kappaB signaling retards eosinophilic dermatitis in SHARPIN-deficient mice[J]. J Invest Dermatol,2011,131(1):141-149.
[35] Rivkin E,Almeida SM,Ceccarelli DF,et al. The linear ubiquitin-specific deubiquitinase gumby regulates angiogenesis[J]. Nature,2013,498(7454):318-324.
[36] Heger K,Wickliffe KE,Ndoja A,et al. OTULIN limits cell death and inflammation by deubiquitinating LUBAC[J]. Nature,2018,559(7712):120-124
[37] Damgaard RB,Walker JA,Marco-Casanova P,et al. The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity[J]. Cell,2016,166(5):1215-1230.e1220.
[38] Fiil BK,Damgaard RB,Wagner SA,et al. OTULIN restricts Met1-linked ubiquitination to control innate immune signaling[J]. Mol Cell,2013,50(6):818-830.
[39] Yang Y,Schmitz R,Mitala J,et al. Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms[J]. Cancer Discov,2014,4(4):480-493.
[40] Grumati P,Dikic I. Germline polymorphisms in RNF31 regulate linear ubiquitination and oncogenic signaling[J]. Cancer Discov,2014,4(4):394-396.
[41] Yang YK,Yang C,Chan W,et al. Molecular Determinants of Scaffold-induced Linear Ubiquitinylation of B Cell Lymphoma/Leukemia 10(Bcl10)during T Cell Receptor and Oncogenic Caspase Recruitment Domain-containing Protein 11(CARD11)Signaling[J]. J Biol Chem,2016,291(50):25921-25936.
[42] Rodgers MA,Bowman JW,Fujita H,et al. The linear ubiquitin assembly complex(LUBAC)is essential for NLRP3 inflammasome activation[J]. J Exp Med,2014,211(7):1333-1347.
[43] Qin Z,Jiang W,Wang G,et al. Linear ubiquitin chain induces apoptosis and inhibits tumor growth[J]. Apoptosis,2017,23(1):16-26.