Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma

Cancer Cell

Volumn 29, Issue 4, 2016, Pages 494-507

  Yang, Yibin ^a   Kelly, Priscilla ^a   Shaffer, Arthur L ^a   Schmitz, Roland ^a   Yoo, Hee Min ^a   Liu, Xinyue ^a   Huang, Da Wei ^a   Webster, Daniel ^a   Young, Ryan M ^a   Nakagawa, Masao ^a   Ceribelli, Michele ^a   Wright, George W ^a   Yang, Yandan ^a   Zhao, Hong ^a   Yu, Xin ^a   Xu, Weihong ^a   Chan, Wing C ^b   Jaffe, Elaine S ^a   Gascoyne, Randy D ^c   Campo, Elias ^d   Rosenwald, Andreas ^e   Ott, German ^f   Delabie, Jan ^g   Rimsza, Lisa ^h   Staudt, Louis M ^a   more..

^a NATIONAL CANCER INSTITUTE   (United States)

^b CITY OF HOPE NATIONAL MEDICAL CENTER   (United States)

^c BRITISH COLUMBIA CANCER AGENCY   (Canada)

^d UNIVERSITY OF BARCELONA   (Spain)

^e UNIVERSITY OF WÜRZBURG   (Germany)

^f ROBERT BOSCH HOSPITAL   (Germany)

^g UNIVERSITY HEALTH NETWORK   (Canada)

^h UNIVERSITY OF ARIZONA COLLEGE OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BIRINAPANT; CIAP1 PROTEIN; CIAP2 PROTEIN; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; LIGASE; LINEAR UBIQUITIN CHAIN LIGASE; POLYUBIQUITIN; PROTEIN BCL 10; UBIQUITIN PROTEIN LIGASE E3; UNCLASSIFIED DRUG; BCL10 PROTEIN, HUMAN; BIRC2 PROTEIN, HUMAN; BIRC3 PROTEIN, HUMAN; CARD11 PROTEIN, HUMAN; CASPASE; CASPASE RECRUITMENT DOMAIN SIGNALING PROTEIN; DIABLO PROTEIN, HUMAN; DIPEPTIDE; FUSED HETEROCYCLIC RINGS; GUANYLATE CYCLASE; I KAPPA B KINASE; INDOLE DERIVATIVE; INHIBITOR OF APOPTOSIS PROTEIN; LYMPHOCYTE ANTIGEN RECEPTOR; MALT1 PROTEIN, HUMAN; MITOCHONDRIAL PROTEIN; MULTIPROTEIN COMPLEX; SIGNAL PEPTIDE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; SM 164; TRIAZOLE DERIVATIVE; TUMOR PROTEIN; UBIQUITIN PROTEIN LIGASE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; GENE DOSAGE; GENE LOCUS; HUMAN; HUMAN CELL; LARGE CELL LYMPHOMA; MOUSE; NONHUMAN; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; UBIQUITINATION; ANIMAL; ANTAGONISTS AND INHIBITORS; B LYMPHOCYTE; CHEMISTRY; CLASSIFICATION; COMPARATIVE STUDY; CRISPR CAS SYSTEM; DRUG EFFECTS; DRUG SCREENING; ENZYME ACTIVATION; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION; GENETICS; LYMPHOMA, LARGE B-CELL, DIFFUSE; METABOLISM; NONOBESE DIABETIC MOUSE; PHYSIOLOGY; PROTEIN PROCESSING; SCID MOUSE; TUMOR CELL LINE;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; B-LYMPHOCYTES; BICYCLO COMPOUNDS, HETEROCYCLIC; CARD SIGNALING ADAPTOR PROTEINS; CASPASES; CELL LINE, TUMOR; CRISPR-CAS SYSTEMS; DIPEPTIDES; ENZYME ACTIVATION; GENE DOSAGE; GENE EXPRESSION PROFILING; GENE EXPRESSION REGULATION, NEOPLASTIC; GUANYLATE CYCLASE; HUMANS; I-KAPPA B KINASE; INDOLES; INHIBITOR OF APOPTOSIS PROTEINS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; LYMPHOMA, LARGE B-CELL, DIFFUSE; MICE; MICE, INBRED NOD; MICE, SCID; MITOCHONDRIAL PROTEINS; MULTIPROTEIN COMPLEXES; NEOPLASM PROTEINS; NF-KAPPA B; PROTEIN PROCESSING, POST-TRANSLATIONAL; RECEPTORS, ANTIGEN, B-CELL; TRIAZOLES; UBIQUITIN-PROTEIN LIGASES; UBIQUITINATION; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84962685404     PISSN: 15356108     EISSN: 18783686     Source Type: Journal    
DOI: 10.1016/j.ccell.2016.03.006     Document Type: Article

References (72)

1. Alizadeh A.A., Eisen M.B., Davis R.E., Ma C., Lossos I.S., Rosenwald A., Boldrick J.C., Sabet H., Tran T., Yu X., et al. Distinct types of diffuse large B-cell lymphoma identified by gene expression profiling. Nature 2000, 403:503-511.
2. Allensworth J.L., Sauer S.J., Lyerly H.K., Morse M.A., Devi G.R. Smac mimetic Birinapant induces apoptosis and enhances TRAIL potency in inflammatory breast cancer cells in an IAP-dependent and TNF-alpha-independent mechanism. Breast Cancer Res. Treat. 2013, 137:359-371.
3. Annunziata C.M., Davis R.E., Demchenko Y., Bellamy W., Gabrea A., Zhan F., Lenz G., Hanamura I., Wright G., Xiao W., et al. Frequent engagement of the classical and alternative NF-kappaB pathways by diverse genetic abnormalities in multiple myeloma. Cancer Cell 2007, 12:115-130.
4. Bea S., Valdes-Mas R., Navarro A., Salaverria I., Martin-Garcia D., Jares P., Gine E., Pinyol M., Royo C., Nadeu F., et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc. Natl. Acad. Sci. USA 2013, 110:18250-18255.
5. Benetatos C.A., Mitsuuchi Y., Burns J.M., Neiman E.M., Condon S.M., Yu G., Seipel M.E., Kapoor G.S., Laporte M.G., Rippin S.R., et al. Birinapant (TL32711), a bivalent SMAC mimetic, targets TRAF2-associated cIAPs, abrogates TNF-induced NF-kappaB activation, and is active in patient-derived xenograft models. Mol. Cancer Ther. 2014, 13:867-879.
6. Bertrand M.J., Milutinovic S., Dickson K.M., Ho W.C., Boudreault A., Durkin J., Gillard J.W., Jaquith J.B., Morris S.J., Barker P.A. cIAP1 and cIAP2 facilitate cancer cell survival by functioning as E3 ligases that promote RIP1 ubiquitination. Mol. Cell 2008, 30:689-700.
7. Blankenship J.W., Varfolomeev E., Goncharov T., Fedorova A.V., Kirkpatrick D.S., Izrael-Tomasevic A., Phu L., Arnott D., Aghajan M., Zobel K., et al. Ubiquitin binding modulates IAP antagonist-stimulated proteasomal degradation of c-IAP1 and c-IAP2(1). Biochem. J. 2009, 417:149-160.
8. Chan W., Schaffer T.B., Pomerantz J.L. A quantitative signaling screen identifies CARD11 mutations in the CARD and LATCH domains that induce Bcl10 ubiquitination and human lymphoma cell survival. Mol. Cell Biol. 2013, 33:429-443.
9. Chen Z.J. Ubiquitination in signaling to and activation of IKK. Immunol. Rev. 2012, 246:95-106.
10. Chu Z.L., McKinsey T.A., Liu L., Gentry J.J., Malim M.H., Ballard D.W. Suppression of tumor necrosis factor-induced cell death by inhibitor of apoptosis c-IAP2 is under NF-kappaB control. Proc. Natl. Acad. Sci. USA 1997, 94:10057-10062.
11. Condon S.M., Mitsuuchi Y., Deng Y., LaPorte M.G., Rippin S.R., Haimowitz T., Alexander M.D., Kumar P.T., Hendi M.S., Lee Y.H., et al. Birinapant, a smac-mimetic with improved tolerability for the treatment of solid tumors and hematological malignancies. J. Med. Chem. 2014, 57:3666-3677.
12. Cong L., Ran F.A., Cox D., Lin S., Barretto R., Habib N., Hsu P.D., Wu X., Jiang W., Marraffini L.A., Zhang F. Multiplex genome engineering using CRISPR/Cas systems. Science 2013, 339:819-823.
13. Davis R.E., Brown K.D., Siebenlist U., Staudt L.M. Constitutive nuclear factor kappa B activity is required for survival of activated B Cell-like diffuse large B cell lymphoma cells. J. Exp. Med. 2001, 194:1861-1874.
14. Davis R.E., Ngo V.N., Lenz G., Tolar P., Young R.M., Romesser P.B., Kohlhammer H., Lamy L., Zhao H., Yang Y., et al. Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma. Nature 2010, 463:88-92.
15. Dueber E.C., Schoeffler A.J., Lingel A., Elliott J.M., Fedorova A.V., Giannetti A.M., Zobel K., Maurer B., Varfolomeev E., Wu P., et al. Antagonists induce a conformational change in cIAP1 that promotes autoubiquitination. Science 2011, 334:376-380.
16. Eckelman B.P., Salvesen G.S. The human anti-apoptotic proteins cIAP1 and cIAP2 bind but do not inhibit caspases. J. Biol. Chem. 2006, 281:3254-3260.
17. Emmerich C.H., Ordureau A., Strickson S., Arthur J.S., Pedrioli P.G., Komander D., Cohen P. Activation of the canonical IKK complex by K63/M1-linked hybrid ubiquitin chains. Proc. Natl. Acad. Sci. USA 2013, 110:15247-15252.
18. Fujita H., Rahighi S., Akita M., Kato R., Sasaki Y., Wakatsuki S., Iwai K. Mechanism underlying IkappaB kinase activation mediated by the linear ubiquitin chain assembly complex. Mol. Cell Biol. 2014, 34:1322-1335.
19. Fulda S., Vucic D. Targeting IAP proteins for therapeutic intervention in cancer. Nat. Rev. Drug Discov. 2012, 11:109-124.
20. Gardam S., Turner V.M., Anderton H., Limaye S., Basten A., Koentgen F., Vaux D.L., Silke J., Brink R. Deletion of cIAP1 and cIAP2 in murine B lymphocytes constitutively activates cell survival pathways and inactivates the germinal center response. Blood 2011, 117:4041-4051.
21. Gerlach B., Cordier S.M., Schmukle A.C., Emmerich C.H., Rieser E., Haas T.L., Webb A.I., Rickard J.A., Anderton H., Wong W.W., et al. Linear ubiquitination prevents inflammation and regulates immune signalling. Nature 2011, 471:591-596.
22. Greco W.R., Park H.S., Rustum Y.M. Application of a new approach for the quantitation of drug synergism to the combination of cis-diamminedichloroplatinum and 1-beta-D-arabinofuranosylcytosine. Cancer Res. 1990, 50:5318-5327.
23. Haas T.L., Emmerich C.H., Gerlach B., Schmukle A.C., Cordier S.M., Rieser E., Feltham R., Vince J., Warnken U., Wenger T., et al. Recruitment of the linear ubiquitin chain assembly complex stabilizes the TNF-R1 signaling complex and is required for TNF-mediated gene induction. Mol. Cell 2009, 36:831-844.
24. Ikeda F., Deribe Y.L., Skanland S.S., Stieglitz B., Grabbe C., Franz-Wachtel M., van Wijk S.J., Goswami P., Nagy V., Terzic J., et al. SHARPIN forms a linear ubiquitin ligase complex regulating NF-kappaB activity and apoptosis. Nature 2011, 471:637-641.
25. Keats J.J., Fonseca R., Chesi M., Schop R., Baker A., Chng W.J., Van Wier S., Tiedemann R., Shi C.X., Sebag M., et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell 2007, 12:131-144.
26. Kensche T., Tokunaga F., Ikeda F., Goto E., Iwai K., Dikic I. Analysis of nuclear factor-kappaB (NF-kappaB) essential modulator (NEMO) binding to linear and lysine-linked ubiquitin chains and its role in the activation of NF-kappaB. J. Biol. Chem. 2012, 287:23626-23634.
27. Krepler C., Chunduru S.K., Halloran M.B., He X., Xiao M., Vultur A., Villanueva J., Mitsuuchi Y., Neiman E.M., Benetatos C., et al. The novel SMAC mimetic birinapant exhibits potent activity against human melanoma cells. Clin. Cancer Res. 2013, 19:1784-1794.
28. Lam L.T., Davis R.E., Pierce J., Hepperle M., Xu Y., Hottelet M., Nong Y., Wen D., Adams J., Dang L., Staudt L.M. Small molecule inhibitors of IkappaB kinase are selectively toxic for subgroups of diffuse large B-cell lymphoma defined by gene expression profiling. Clin. Cancer Res. 2005, 11:28-40.
29. Lenz G., Davis R.E., Ngo V.N., Lam L., George T.C., Wright G.W., Dave S.S., Zhao H., Xu W., Rosenwald A., et al. Oncogenic CARD11 mutations in human diffuse large B cell lymphoma. Science 2008, 319:1676-1679.
30. Lenz G., Wright G.W., Emre N.C., Kohlhammer H., Dave S.S., Davis R.E., Carty S., Lam L.T., Shaffer A.L., Xiao W., et al. Molecular subtypes of diffuse large B-cell lymphoma arise by distinct genetic pathways. Proc. Natl. Acad. Sci. USA 2008, 105:13520-13525.
31. Liston P., Roy N., Tamai K., Lefebvre C., Baird S., Cherton-Horvat G., Farahani R., McLean M., Ikeda J.E., MacKenzie A., Korneluk R.G. Suppression of apoptosis in mammalian cells by NAIP and a related family of IAP genes. Nature 1996, 379:349-353.
32. Lohr J.G., Stojanov P., Lawrence M.S., Auclair D., Chapuy B., Sougnez C., Cruz-Gordillo P., Knoechel B., Asmann Y.W., Slager S.L., et al. Discovery and prioritization of somatic mutations in diffuse large B-cell lymphoma (DLBCL) by whole-exome sequencing. Proc. Natl. Acad. Sci. USA 2012, 109:3879-3884.
33. Mali P., Yang L., Esvelt K.M., Aach J., Guell M., DiCarlo J.E., Norville J.E., Church G.M. RNA-guided human genome engineering via Cas9. Science 2013, 339:823-826.
34. Mathews Griner L.A., Guha R., Shinn P., Young R.M., Keller J.M., Liu D., Goldlust I.S., Yasgar A., McKnight C., Boxer M.B., et al. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells. Proc. Natl. Acad. Sci. USA 2014, 111:2349-2354.
35. Micheau O., Tschopp J. Induction of TNF receptor I-mediated apoptosis via two sequential signaling complexes. Cell 2003, 114:181-190.
36. Morin R.D., Mendez-Lago M., Mungall A.J., Goya R., Mungall K.L., Corbett R.D., Johnson N.A., Severson T.M., Chiu R., Field M., et al. Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma. Nature 2011, 476:298-303.
37. Ngadjeua F., Chiaravalli J., Traincard F., Raynal B., Fontan E., Agou F. Two-sided ubiquitin binding of NF-kappaB essential modulator (NEMO) zinc finger unveiled by a mutation associated with anhidrotic ectodermal dysplasia with immunodeficiency syndrome. J. Biol. Chem. 2013, 288:33722-33737.
38. Ngo V.N., Davis R.E., Lamy L., Yu X., Zhao H., Lenz G., Lam L.T., Dave S., Yang L., Powell J., Staudt L.M. A loss-of-function RNA interference screen for molecular targets in cancer. Nature 2006, 441:106-110.
39. Ngo V.N., Young R.M., Schmitz R., Jhavar S., Xiao W., Lim K.H., Kohlhammer H., Xu W., Yang Y., Zhao H., et al. Oncogenically active MYD88 mutations in human lymphoma. Nature 2011, 470:115-119.
40. Oeckinghaus A., Wegener E., Welteke V., Ferch U., Arslan S.C., Ruland J., Scheidereit C., Krappmann D. Malt1 ubiquitination triggers NF-kappaB signaling upon T-cell activation. EMBO J. 2007, 26:4634-4645.
41. Park S.M., Yoon J.B., Lee T.H. Receptor interacting protein is ubiquitinated by cellular inhibitor of apoptosis proteins (c-IAP1 and c-IAP2) in vitro. FEBS Lett. 2004, 566:151-156.
42. Pasqualucci L., Trifonov V., Fabbri G., Ma J., Rossi D., Chiarenza A., Wells V.A., Grunn A., Messina M., Elliot O., et al. Analysis of the coding genome of diffuse large B-cell lymphoma. Nat. Genet. 2011, 43:830-837.
43. Puente X.S., Bea S., Valdes-Mas R., Villamor N., Gutierrez-Abril J., Martin-Subero J.I., Munar M., Rubio-Perez C., Jares P., Aymerich M., et al. Non-coding recurrent mutations in chronic lymphocytic leukaemia. Nature 2015, 526:519-524.
44. Rahal R., Frick M., Romero R., Korn J.M., Kridel R., Chan F.C., Meissner B., Bhang H.E., Ruddy D., Kauffmann A., et al. Pharmacological and genomic profiling identifies NF-kappaB-targeted treatment strategies for mantle cell lymphoma. Nat. Med. 2014, 20:87-92.
45. Rossi D., Trifonov V., Fangazio M., Bruscaggin A., Rasi S., Spina V., Monti S., Vaisitti T., Arruga F., Fama R., et al. The coding genome of splenic marginal zone lymphoma: activation of NOTCH2 and other pathways regulating marginal zone development. J. Exp. Med. 2012, 209:1537-1551.
46. Rothe M., Pan M.G., Henzel W.J., Ayres T.M., Goeddel D.V. The TNFR2-TRAF signaling complex contains two novel proteins related to baculoviral inhibitor of apoptosis proteins. Cell 1995, 83:1243-1252.
47. Roy N., Deveraux Q.L., Takahashi R., Salvesen G.S., Reed J.C. The c-IAP-1 and c-IAP-2 proteins are direct inhibitors of specific caspases. EMBO J. 1997, 16:6914-6925.
48. Samuel T., Welsh K., Lober T., Togo S.H., Zapata J.M., Reed J.C. Distinct BIR domains of cIAP1 mediate binding to and ubiquitination of tumor necrosis factor receptor-associated factor 2 and second mitochondrial activator of caspases. J. Biol. Chem. 2006, 281:1080-1090.
49. Satpathy S., Wagner S.A., Beli P., Gupta R., Kristiansen T.A., Malinova D., Francavilla C., Tolar P., Bishop G.A., Hostager B.S., Choudhary C. Systems-wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation. Mol. Syst. Biol. 2015, 11:810.
50. Scholtysik R., Kreuz M., Hummel M., Rosolowski M., Szczepanowski M., Klapper W., Loeffler M., Trumper L., Siebert R., Kuppers R., et al. Characterization of genomic imbalances in diffuse large B-cell lymphoma by detailed SNP-chip analysis. Int. J. Cancer 2015, 136:1033-1042.
51. Shaffer A.L., Wright G., Yang L., Powell J., Ngo V., Lamy L., Lam L.T., Davis R.E., Staudt L.M. A library of gene expression signatures to illuminate normal and pathological lymphoid biology. Immunol. Rev. 2006, 210:67-85.
52. Shaffer A.L., Young R.M., Staudt L.M. Pathogenesis of human B cell lymphomas. Annu. Rev. Immunol. 2012, 30:565-610.
53. Shalem O., Sanjana N.E., Hartenian E., Shi X., Scott D.A., Mikkelsen T.S., Heckl D., Ebert B.L., Root D.E., Doench J.G., Zhang F. Genome-scale CRISPR-Cas9 knockout screening in human cells. Science 2014, 343:84-87.
54. Shu H.B., Takeuchi M., Goeddel D.V. The tumor necrosis factor receptor 2 signal transducers TRAF2 and c-IAP1 are components of the tumor necrosis factor receptor 1 signaling complex. Proc. Natl. Acad. Sci. USA 1996, 93:13973-13978.
55. Silva G.M., Finley D., Vogel C. K63 polyubiquitination is a new modulator of the oxidative stress response. Nat. Struct. Mol. Biol. 2015, 22:116-123.
56. Sun L., Deng L., Ea C.K., Xia Z.P., Chen Z.J. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol. Cell 2004, 14:289-301.
57. Vallabhapurapu S., Matsuzawa A., Zhang W., Tseng P.H., Keats J.J., Wang H., Vignali D.A., Bergsagel P.L., Karin M. Nonredundant and complementary functions of TRAF2 and TRAF3 in a ubiquitination cascade that activates NIK-dependent alternative NF-kappaB signaling. Nat. Immunol. 2008, 9:1364-1370.
58. Varfolomeev E., Blankenship J.W., Wayson S.M., Fedorova A.V., Kayagaki N., Garg P., Zobel K., Dynek J.N., Elliott L.O., Wallweber H.J., et al. IAP antagonists induce autoubiquitination of c-IAPs, NF-kappaB activation, and TNFalpha-dependent apoptosis. Cell 2007, 131:669-681.
59. Varfolomeev E., Goncharov T., Fedorova A.V., Dynek J.N., Zobel K., Deshayes K., Fairbrother W.J., Vucic D. c-IAP1 and c-IAP2 are critical mediators of tumor necrosis factor alpha (TNFalpha)-induced NF-kappaB activation. J. Biol. Chem. 2008, 283:24295-24299.
60. Vince J.E., Wong W.W., Khan N., Feltham R., Chau D., Ahmed A.U., Benetatos C.A., Chunduru S.K., Condon S.M., McKinlay M., et al. IAP antagonists target cIAP1 to induce TNFalpha-dependent apoptosis. Cell 2007, 131:682-693.
61. Walczak H., Iwai K., Dikic I. Generation and physiological roles of linear ubiquitin chains. BMC Biol. 2012, 10:23.
62. Wang C.Y., Mayo M.W., Korneluk R.G., Goeddel D.V., Baldwin A.S. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science 1998, 281:1680-1683.
63. Wang T., Wei J.J., Sabatini D.M., Lander E.S. Genetic screens in human cells using the CRISPR-Cas9 system. Science 2014, 343:80-84.
64. Wilson W.H., Young R.M., Schmitz R., Yang Y., Pittaluga S., Wright G., Lih C.J., Williams P.M., Shaffer A.L., Gerecitano J., et al. Targeting B cell receptor signaling with ibrutinib in diffuse large B cell lymphoma. Nat. Med. 2015, 21:922-926.
65. Wu C.J., Ashwell J.D. NEMO recognition of ubiquitinated Bcl10 is required for T cell receptor-mediated NF-kappaB activation. Proc. Natl. Acad. Sci. USA 2008, 105:3023-3028.
66. Wu C.J., Conze D.B., Li T., Srinivasula S.M., Ashwell J.D. Sensing of Lys 63-linked polyubiquitination by NEMO is a key event in NF-kappaB activation [corrected]. Nat. Cell Biol. 2006, 8:398-406.
67. Yang Y., Fang S., Jensen J.P., Weissman A.M., Ashwell J.D. Ubiquitin protein ligase activity of IAPs and their degradation in proteasomes in response to apoptotic stimuli. Science 2000, 288:874-877.
68. Yang Y., Schmitz R., Mitala J., Whiting A., Xiao W., Ceribelli M., Wright G.W., Zhao H., Yang Y., Xu W., et al. Essential role of the linear ubiquitin chain assembly complex in lymphoma revealed by rare germline polymorphisms. Cancer Discov. 2014, 4:480-493.
69. Zarnegar B., Yamazaki S., He J.Q., Cheng G. Control of canonical NF-kappaB activation through the NIK-IKK complex pathway. Proc. Natl. Acad. Sci. USA 2008, 105:3503-3508.
70. Zarnegar B.J., Wang Y., Mahoney D.J., Dempsey P.W., Cheung H.H., He J., Shiba T., Yang X., Yeh W.C., Mak T.W., et al. Noncanonical NF-kappaB activation requires coordinated assembly of a regulatory complex of the adaptors cIAP1, cIAP2, TRAF2 and TRAF3 and the kinase NIK. Nat. Immunol. 2008, 9:1371-1378.
71. Zhang J., Grubor V., Love C.L., Banerjee A., Richards K.L., Mieczkowski P.A., Dunphy C., Choi W., Au W.Y., Srivastava G., et al. Genetic heterogeneity of diffuse large B-cell lymphoma. Proc. Natl. Acad. Sci. USA 2013, 110:1398-1403.
72. Zhang B., Calado D.P., Wang Z., Frohler S., Kochert K., Qian Y., Koralov S.B., Schmidt-Supprian M., Sasaki Y., Unitt C., et al. An oncogenic role for alternative NF-kappaB signaling in DLBCL revealed upon deregulated BCL6 expression. Cell Rep. 2015, 11:715-726.