tnf receptor associated factor 2


Summary: A signal transducing tumor necrosis factor receptor associated factor that is involved in TNF RECEPTOR feedback regulation. It is similar in structure and appears to work in conjunction with TNF RECEPTOR-ASSOCIATED FACTOR 1 to inhibit APOPTOSIS.

Top Publications

  1. Eliopoulos A, Blake S, Floettmann J, Rowe M, Young L. Epstein-Barr virus-encoded latent membrane protein 1 activates the JNK pathway through its extreme C terminus via a mechanism involving TRADD and TRAF2. J Virol. 1999;73:1023-35 pubmed
    ..These data further define a role for TRADD and TRAF2 in JNK activation and confirm that LMP1 utilizes signalling mechanisms used by the TNF receptor/CD40 family to elicit its pleiotropic activities. ..
  2. Sun L, Deng L, Ea C, Xia Z, Chen Z. The TRAF6 ubiquitin ligase and TAK1 kinase mediate IKK activation by BCL10 and MALT1 in T lymphocytes. Mol Cell. 2004;14:289-301 pubmed
    ..These results reveal an oligomerization --> ubiquitination --> phosphorylation cascade that culminates in NF-kappaB activation in T lymphocytes. ..
  3. Kobayashi N, Kadono Y, Naito A, Matsumoto K, Yamamoto T, Tanaka S, et al. Segregation of TRAF6-mediated signaling pathways clarifies its role in osteoclastogenesis. EMBO J. 2001;20:1271-80 pubmed
    ..Thus, TRAF6 plays essential roles in both the differentiation and maturation of osteoclasts by activating various kinases via its multiple domains. ..
  4. Darnay B, Ni J, Moore P, Aggarwal B. Activation of NF-kappaB by RANK requires tumor necrosis factor receptor-associated factor (TRAF) 6 and NF-kappaB-inducing kinase. Identification of a novel TRAF6 interaction motif. J Biol Chem. 1999;274:7724-31 pubmed
  5. Trompouki E, Hatzivassiliou E, Tsichritzis T, Farmer H, Ashworth A, Mosialos G. CYLD is a deubiquitinating enzyme that negatively regulates NF-kappaB activation by TNFR family members. Nature. 2003;424:793-6 pubmed
    ..These results indicate that CYLD is a negative regulator of the cytokine-mediated activation of NF-kappaB that is required for appropriate cellular homeostasis of skin appendages. ..
  6. Kuai J, Nickbarg E, Wooters J, Qiu Y, Wang J, Lin L. Endogenous association of TRAF2, TRAF3, cIAP1, and Smac with lymphotoxin beta receptor reveals a novel mechanism of apoptosis. J Biol Chem. 2003;278:14363-9 pubmed
    ..Their association with LT beta R was further confirmed by coimmunoprecipitation in U937 cells and HEK293 cells. The presence of cIAP1 and Smac in LIGHT.LT beta R complex revealed a novel mechanism of LIGHT.LT beta R-induced apoptosis. ..
  7. Brown S, Richards C, Hanscom H, Feng S, Winkles J. The Fn14 cytoplasmic tail binds tumour-necrosis-factor-receptor-associated factors 1, 2, 3 and 5 and mediates nuclear factor-kappaB activation. Biochem J. 2003;371:395-403 pubmed
    ..These results indicate that Fn14 is a functional TWEAK receptor that can associate with four distinct TRAF family members and stimulate the NF-kappaB transcription factor signalling pathway. ..
  8. Horie R, Watanabe T, Ito K, Morisita Y, Watanabe M, Ishida T, et al. Cytoplasmic aggregation of TRAF2 and TRAF5 proteins in the Hodgkin-Reed-Sternberg cells. Am J Pathol. 2002;160:1647-54 pubmed
    ..Thus, cytoplasmic aggregation of TRAF proteins appears to reflect constitutive CD30 signaling which is characteristic of H-RS cells. ..
  9. Samuel T, Welsh K, Lober T, Togo S, Zapata J, Reed J. 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;281:1080-90 pubmed

More Information


  1. Nguyen L, Duncan G, Mirtsos C, Ng M, Speiser D, Shahinian A, et al. TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses. Immunity. 1999;11:379-89 pubmed
    ..These data demonstrate two important roles of TRAF2, one as a negative regulator of certain TNFR1 signals and the other as a positive mediator of CD40 signaling. ..
  2. Tada K, Okazaki T, Sakon S, Kobarai T, Kurosawa K, Yamaoka S, et al. Critical roles of TRAF2 and TRAF5 in tumor necrosis factor-induced NF-kappa B activation and protection from cell death. J Biol Chem. 2001;276:36530-4 pubmed
    ..Collectively, these results indicate that both TRAF2 and TRAF5 are involved in TNF-induced NF-kappaB activation and protection from cell death. ..
  3. Wang C, Mayo M, Korneluk R, Goeddel D, Baldwin A. NF-kappaB antiapoptosis: induction of TRAF1 and TRAF2 and c-IAP1 and c-IAP2 to suppress caspase-8 activation. Science. 1998;281:1680-3 pubmed
    ..Thus, NF-kappaB activates a group of gene products that function cooperatively at the earliest checkpoint to suppress TNF-alpha-mediated apoptosis and that function more distally to suppress genotoxic agent-mediated apoptosis. ..
  4. Noguchi T, Takeda K, Matsuzawa A, Saegusa K, Nakano H, Gohda J, et al. Recruitment of tumor necrosis factor receptor-associated factor family proteins to apoptosis signal-regulating kinase 1 signalosome is essential for oxidative stress-induced cell death. J Biol Chem. 2005;280:37033-40 pubmed
    ..A novel signaling complex including TRAF2, TRAF6, and ASK1 may thus be the key component in oxidative stress-induced cell death. ..
  5. Munroe M, Bishop G. Role of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) in distinct and overlapping CD40 and TNF receptor 2/CD120b-mediated B lymphocyte activation. J Biol Chem. 2004;279:53222-31 pubmed
    ..CD40 and CD120b used primarily divergent mechanisms to activate NF-kappaB, exemplifying how TNFR family members can use diverse mechanisms to mediate similar downstream events. ..
  6. Kovalenko A, Chable Bessia C, Cantarella G, Israel A, Wallach D, Courtois G. The tumour suppressor CYLD negatively regulates NF-kappaB signalling by deubiquitination. Nature. 2003;424:801-5 pubmed
    ..Truncations of CYLD found in cylindromatosis result in reduced enzymatic activity, indicating a link between impaired deubiquitination of CYLD substrates and human pathophysiology. ..
  7. Vince J, Chau D, Callus B, Wong W, Hawkins C, Schneider P, et al. TWEAK-FN14 signaling induces lysosomal degradation of a cIAP1-TRAF2 complex to sensitize tumor cells to TNFalpha. J Cell Biol. 2008;182:171-84 pubmed publisher
    ..Lysosomal degradation of cIAP1-TRAF2 by TWEAK/FN14 therefore critically alters the balance of life/death signals emanating from TNF-R1 in immortalized cells. ..
  8. Xia P, Wang L, Moretti P, Albanese N, Chai F, Pitson S, et al. Sphingosine kinase interacts with TRAF2 and dissects tumor necrosis factor-alpha signaling. J Biol Chem. 2002;277:7996-8003 pubmed
    ..These findings show a role for SphK in the signal transduction by TRAF2 specifically leading to activation of NF-kappa B and antiapoptosis. ..
  9. Massoumi R, Chmielarska K, Hennecke K, Pfeifer A, Fassler R. Cyld inhibits tumor cell proliferation by blocking Bcl-3-dependent NF-kappaB signaling. Cell. 2006;125:665-77 pubmed
  10. Leonardi A, Ellinger Ziegelbauer H, Franzoso G, Brown K, Siebenlist U. Physical and functional interaction of filamin (actin-binding protein-280) and tumor necrosis factor receptor-associated factor 2. J Biol Chem. 2000;275:271-8 pubmed
    ..Reintroduction of Filamin into these cells restores the TNF response. The data imply a role for Filamin in inflammatory signal transduction pathways. ..
  11. Malinin N, Boldin M, Kovalenko A, Wallach D. MAP3K-related kinase involved in NF-kappaB induction by TNF, CD95 and IL-1. Nature. 1997;385:540-4 pubmed
    ..It also blocked NF-kappaB induction by interleukin-1. Our findings indicate that NIK participates in an NF-kappaB-inducing signalling cascade common to receptors of the TNF/NGF family and to the interleukin-1 type-I receptor. ..
  12. Ye H, Park Y, Kreishman M, Kieff E, Wu H. The structural basis for the recognition of diverse receptor sequences by TRAF2. Mol Cell. 1999;4:321-30 pubmed
    ..The structural information provides a template for the further dissection of receptor binding specificity of TRAF2 and for the understanding of the complexity of TRAF-mediated signal transduction. ..
  13. Yeh W, Shahinian A, Speiser D, Kraunus J, Billia F, Wakeham A, et al. Early lethality, functional NF-kappaB activation, and increased sensitivity to TNF-induced cell death in TRAF2-deficient mice. Immunity. 1997;7:715-25 pubmed
    ..These results suggest that TRAF2-independent pathways of NF-kappaB activation exist and that TRAF2 is required for an NF-kappaB-independent signal that protects against TNF-induced apoptosis. ..
  14. Baud V, Liu Z, Bennett B, Suzuki N, Xia Y, Karin M. Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. Genes Dev. 1999;13:1297-308 pubmed
    ..TNF-alpha also enhances the binding of native TRAF2 to MEKK1 and stimulates the kinase activity of the latter. Thus, TNF-alpha and IL-1 signaling is based on oligomerization of TRAF2 and TRAF6 leading to activation of effector kinases. ..
  15. Song H, Regnier C, Kirschning C, Goeddel D, Rothe M. Tumor necrosis factor (TNF)-mediated kinase cascades: bifurcation of nuclear factor-kappaB and c-jun N-terminal kinase (JNK/SAPK) pathways at TNF receptor-associated factor 2. Proc Natl Acad Sci U S A. 1997;94:9792-6 pubmed
    ..Thus, TRAF2 is the bifurcation point of two kinase cascades leading to activation of NF-kappaB and JNK, respectively. ..
  16. Boucher L, Marengere L, Lu Y, Thukral S, Mak T. Binding sites of cytoplasmic effectors TRAF1, 2, and 3 on CD30 and other members of the TNF receptor superfamily. Biochem Biophys Res Commun. 1997;233:592-600 pubmed
    ..We show that these amino acid motifs are conserved in TNFRp75 and CD40 and that sequences in these receptors homologous to TRAF-binding sequences found in CD30 can selectively bind the TRAFs in a predictable manner. ..
  17. Grech A, Amesbury M, Chan T, Gardam S, Basten A, Brink R. TRAF2 differentially regulates the canonical and noncanonical pathways of NF-kappaB activation in mature B cells. Immunity. 2004;21:629-42 pubmed
    ..This dual functionality explains the contrasting roles of TRAF2 in B cell maturation and activation. ..
  18. Zirlik A, Bavendiek U, Libby P, MacFarlane L, Gerdes N, Jagielska J, et al. TRAF-1, -2, -3, -5, and -6 are induced in atherosclerotic plaques and differentially mediate proinflammatory functions of CD40L in endothelial cells. Arterioscler Thromb Vasc Biol. 2007;27:1101-7 pubmed
    ..These results implicate endothelial TRAF-1, -2, -3, -5, and -6 in CD40 signaling in atherogenesis, identifying these molecules as potential targets for selective therapeutic intervention. ..
  19. Fotin Mleczek M, Henkler F, Samel D, Reichwein M, Hausser A, Parmryd I, et al. Apoptotic crosstalk of TNF receptors: TNF-R2-induces depletion of TRAF2 and IAP proteins and accelerates TNF-R1-dependent activation of caspase-8. J Cell Sci. 2002;115:2757-70 pubmed
    ..Hence, TNF-R2 triggering can interfere with TNF-R1-induced apoptosis by inhibition of NF-kappaB-dependent production of anti-apoptotic factors and by blocking the action of anti-apoptotic factors at the post-transcriptional level. ..
  20. Jang I, Lee Z, Kim Y, Kim S, Kwon B. Human 4-1BB (CD137) signals are mediated by TRAF2 and activate nuclear factor-kappa B. Biochem Biophys Res Commun. 1998;242:613-20 pubmed
    ..4-1BB-mediated NF-kappa B activation was inhibited by a dominant negative-TRAF2 or -NF-kappa B-inducing kinase (NIK). These data suggest that 4-1BB functions may be mediated by NF-kappa B activation, which requires a TRAF2/NIK pathway. ..
  21. Wu C, Conze D, Li X, Ying S, Hanover J, Ashwell J. TNF-alpha induced c-IAP1/TRAF2 complex translocation to a Ubc6-containing compartment and TRAF2 ubiquitination. EMBO J. 2005;24:1886-98 pubmed
    ..Therefore, the ER plays a key role in the TNF-R-mediated signal transduction cascade by acting as a site of assembly for E2/E3/substrate complexes. ..
  22. Park Y, Burkitt V, Villa A, Tong L, Wu H. Structural basis for self-association and receptor recognition of human TRAF2. Nature. 1999;398:533-8 pubmed
    ..The trimeric structure of the TRAF domain provides an avidity-based explanation for the dependence of TRAF recruitment on the oligomerization of the receptors by their trimeric extracellular ligands. ..
  23. Brown K, Hostager B, Bishop G. Differential signaling and tumor necrosis factor receptor-associated factor (TRAF) degradation mediated by CD40 and the Epstein-Barr virus oncoprotein latent membrane protein 1 (LMP1). J Exp Med. 2001;193:943-54 pubmed
    ..This suggests that LMP1 utilizes a modified CD40 signaling pathway. Failure to regulate TRAFs may contribute to the enhanced capacity of LMP1 to activate B cells as well as promote B cell transformation. ..
  24. Hostager B, Bishop G. Cutting edge: contrasting roles of TNF receptor-associated factor 2 (TRAF2) and TRAF3 in CD40-activated B lymphocyte differentiation. J Immunol. 1999;162:6307-11 pubmed
    ..In contrast, TRAF2 appears to play a positive role in B cell differentiation, and this activity is apparent even when its binding site on CD40 is disrupted. ..
  25. Arch R, Gedrich R, Thompson C. Translocation of TRAF proteins regulates apoptotic threshold of cells. Biochem Biophys Res Commun. 2000;272:936-45 pubmed
    ..The ratio between soluble and insoluble TRAF2 determines the sensitivity of cells to TNF-alpha-induced apoptosis and may play an important role in limiting further TRAF-dependent signal transduction. ..
  26. Speiser D, Lee S, Wong B, Arron J, Santana A, Kong Y, et al. A regulatory role for TRAF1 in antigen-induced apoptosis of T cells. J Exp Med. 1997;185:1777-83 pubmed
  27. Hostager B, Haxhinasto S, Rowland S, Bishop G. Tumor necrosis factor receptor-associated factor 2 (TRAF2)-deficient B lymphocytes reveal novel roles for TRAF2 in CD40 signaling. J Biol Chem. 2003;278:45382-90 pubmed
    ..These findings demonstrate previously unappreciated roles for TRAF2 in signaling by TNF receptor family members, using an approach that facilitates the analysis of genes critical to the viability of whole organisms. ..
  28. McWhirter S, Pullen S, Holton J, Crute J, Kehry M, Alber T. Crystallographic analysis of CD40 recognition and signaling by human TRAF2. Proc Natl Acad Sci U S A. 1999;96:8408-13 pubmed
    ..The spacing between the CD40 binding sites on TRAF2 supports an elegant signaling mechanism in which trimeric, extracellular ligands preorganize the receptors to simultaneously recognize three sites on the TRAF trimer. ..
  29. Mukundan L, Bishop G, Head K, Zhang L, Wahl L, Suttles J. TNF receptor-associated factor 6 is an essential mediator of CD40-activated proinflammatory pathways in monocytes and macrophages. J Immunol. 2005;174:1081-90 pubmed
    ..These data demonstrate that TRAF6 acts as a critical adapter of both the Src/ERK1/2 and IKK/NF-kappaB proinflammatory signaling pathways in monocytes and macrophages. ..
  30. Yuasa T, Ohno S, Kehrl J, Kyriakis J. Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein . J Biol Chem. 1998;273:22681-92 pubmed
    ..Thus, TRAF2 initiates SAPK and p38 activation by binding two proximal protein kinases: GCK and RIP. GCK and RIP, in turn, signal by binding MAPKKKs upstream of the SAPKs and p38s. ..
  31. Hostager B, Catlett I, Bishop G. Recruitment of CD40 and tumor necrosis factor receptor-associated factors 2 and 3 to membrane microdomains during CD40 signaling. J Biol Chem. 2000;275:15392-8 pubmed
  32. Benson R, Hostager B, Bishop G. Rapid CD40-mediated rescue from CD95-induced apoptosis requires TNFR-associated factor-6 and PI3K. Eur J Immunol. 2006;36:2535-43 pubmed
    ..In contrast, CD40 rescue was completely abrogated in TRAF6-deficient B cells, which showed reduced activation of Akt in response to CD40 engagement. These results reveal a new rapid mechanism to balance B cell activation and apoptosis. ..
  33. He L, Grammer A, Wu X, Lipsky P. TRAF3 forms heterotrimers with TRAF2 and modulates its ability to mediate NF-{kappa}B activation. J Biol Chem. 2004;279:55855-65 pubmed
    ..Together, these results reveal a novel association between TRAF2 and TRAF3 that is mediated by unique portions of each protein and that specifically regulates activation of NF-kappaB, but not AP-1. ..
  34. Horie R, Watanabe T, Morishita Y, Ito K, Ishida T, Kanegae Y, et al. Ligand-independent signaling by overexpressed CD30 drives NF-kappaB activation in Hodgkin-Reed-Sternberg cells. Oncogene. 2002;21:2493-503 pubmed
    ..Inhibition of NF-kappaB activation by adenovirus vector-mediated gene transfer may provide a novel strategy of cell- and target molecule-specific therapy for patients with HD. ..
  35. Lee S, Choi Y. TRAF-interacting protein (TRIP): a novel component of the tumor necrosis factor receptor (TNFR)- and CD30-TRAF signaling complexes that inhibits TRAF2-mediated NF-kappaB activation. J Exp Med. 1997;185:1275-85 pubmed
    ..Thus, TRIP acts as a receptor-proximal regulator that may influence signals responsible for cell activation/proliferation and cell death induced by members of the TNFR superfamily. ..
  36. Duckett C, Thompson C. CD30-dependent degradation of TRAF2: implications for negative regulation of TRAF signaling and the control of cell survival. Genes Dev. 1997;11:2810-21 pubmed
    ..These studies provide a potential mechanism through which CD30, as well as other TRAF-binding members of the TNFR superfamily, can negatively regulate cell survival. ..
  37. Shi C, Kehrl J. Tumor necrosis factor (TNF)-induced germinal center kinase-related (GCKR) and stress-activated protein kinase (SAPK) activation depends upon the E2/E3 complex Ubc13-Uev1A/TNF receptor-associated factor 2 (TRAF2). J Biol Chem. 2003;278:15429-34 pubmed
    ..These results indicate that the assembly of a TRAF2 lysine 63-linked polyubiquitin chain by Ubc13/Uev1A is required for TNF-mediated GCKR and SAPK activation, but may not be required for ASK1 activation. ..
  38. Chung J, Park Y, Ye H, Wu H. All TRAFs are not created equal: common and distinct molecular mechanisms of TRAF-mediated signal transduction. J Cell Sci. 2002;115:679-88 pubmed
    ..We raise additional questions and propose hypotheses regarding the molecular basis of TRAF signaling specificity. ..
  39. Yin Q, Lamothe B, Darnay B, Wu H. Structural basis for the lack of E2 interaction in the RING domain of TRAF2. Biochemistry. 2009;48:10558-67 pubmed publisher
    ..Our structural observation should prompt a re-evaluation of the role of TRAF2 in TNFalpha signaling and may indicate that TRAF2-associated proteins such as cIAPs may be the ubiquitin ligases for NF-kappaB signaling. ..
  40. Korchnak A, Zhan Y, Aguilar M, Chadee D. Cytokine-induced activation of mixed lineage kinase 3 requires TRAF2 and TRAF6. Cell Signal. 2009;21:1620-5 pubmed publisher
    ..These results reveal a novel mechanism for MLK3 activation by the pro-inflammatory cytokines TNF and IL-1 beta. ..
  41. Keats J, Fonseca R, Chesi M, Schop R, Baker A, Chng W, et al. Promiscuous mutations activate the noncanonical NF-kappaB pathway in multiple myeloma. Cancer Cell. 2007;12:131-44 pubmed
    ..These results highlight the critical importance of the NF-kappaB pathway in the pathogenesis of multiple myeloma. ..
  42. Xie P, Hostager B, Munroe M, Moore C, Bishop G. Cooperation between TNF receptor-associated factors 1 and 2 in CD40 signaling. J Immunol. 2006;176:5388-400 pubmed
  43. Brown K, Hostager B, Bishop G. Regulation of TRAF2 signaling by self-induced degradation. J Biol Chem. 2002;277:19433-8 pubmed
    ..Several approaches show that ubiquitination and proteasomal activity are integral to TRAF2 degradation, and inhibition of this process potentiates CD40 signaling. ..
  44. Natoli G, Costanzo A, Ianni A, Templeton D, Woodgett J, Balsano C, et al. Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science. 1997;275:200-3 pubmed
    ..Therefore, SAPK activation occurs through a pathway that is not required for TNF-R1-induced apoptosis. ..
  45. Sawanobori M, Yamaguchi S, Hasegawa M, Inoue M, Suzuki K, Kamiyama R, et al. Expression of TNF receptors and related signaling molecules in the bone marrow from patients with myelodysplastic syndromes. Leuk Res. 2003;27:583-91 pubmed
  46. Zapata J, Krajewska M, Morse H, Choi Y, Reed J. TNF receptor-associated factor (TRAF) domain and Bcl-2 cooperate to induce small B cell lymphoma/chronic lymphocytic leukemia in transgenic mice. Proc Natl Acad Sci U S A. 2004;101:16600-5 pubmed
    ..Given that many human chronic lymphocytic leukemias overexpress TRAF1 and Bcl-2, our findings suggest that cooperation between Bcl-2 and TRAF pathways contributes to the development of this type of leukemia. ..
  47. Feng X, Gaeta M, Madge L, Yang J, Bradley J, Pober J. Caveolin-1 associates with TRAF2 to form a complex that is recruited to tumor necrosis factor receptors. J Biol Chem. 2001;276:8341-9 pubmed
    ..These findings suggest that intracellular distribution of activated TNF receptors may be regulated by caveolin-1 via its interaction with TRAF2. ..
  48. Wong B, Josien R, Lee S, Vologodskaia M, Steinman R, Choi Y. The TRAF family of signal transducers mediates NF-kappaB activation by the TRANCE receptor. J Biol Chem. 1998;273:28355-9 pubmed
    ..Furthermore, transfection experiments with TRANCE-R deletion mutants revealed that multiple regions of the TRANCE-R can mediate NF-kappaB activation. ..
  49. Kataoka T, Tschopp J. N-terminal fragment of c-FLIP(L) processed by caspase 8 specifically interacts with TRAF2 and induces activation of the NF-kappaB signaling pathway. Mol Cell Biol. 2004;24:2627-36 pubmed
    ..Thus, our present results demonstrate that FLIP(p43) processed by caspase 8 specifically interacts with TRAF2 and subsequently induces activation of the NF-kappaB signaling pathway. ..
  50. Lee T, Shank J, Cusson N, Kelliher M. The kinase activity of Rip1 is not required for tumor necrosis factor-alpha-induced IkappaB kinase or p38 MAP kinase activation or for the ubiquitination of Rip1 by Traf2. J Biol Chem. 2004;279:33185-91 pubmed
    ..Finally, recruitment of the ubiquitinated Tak1 complex is dependent on the presence of Rip1, suggesting that Rip1 ubiquitination rather than its phosphorylation is critical in signaling. ..
  51. Horie R, Watanabe M, Ishida T, Koiwa T, Aizawa S, Itoh K, et al. The NPM-ALK oncoprotein abrogates CD30 signaling and constitutive NF-kappaB activation in anaplastic large cell lymphoma. Cancer Cell. 2004;5:353-64 pubmed
    ..Thus, NPM-ALK abrogates CD30-driven NF-kappaB activation and can also induce an ALCL phenotype, distinguishing ALCL cells from H-RS cells of T cell origin. ..
  52. Brummelkamp T, Nijman S, Dirac A, Bernards R. Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature. 2003;424:797-801 pubmed
    ..We show that this effect can be relieved by aspirin derivatives that inhibit NF-kappaB activity, which suggests a therapeutic intervention strategy to restore growth control in patients suffering from familial cylindromatosis. ..