Cbl-b mediates TGFβ sensitivity by downregulating inhibitory SMAD7 in primary T cells

Journal of Molecular Cell Biology

Volumn 5, Issue 6, 2013, Pages 358-368

  Gruber, Thomas ^a   Hinterleitner, Reinhard ^a   Hermann Kleiter, Natascha ^a   Meisel, Marlies ^a   Kleiter, Ingo ^b   Wang, Chiuhui Mary ^c   Viola, Antonella ^c   Pfeifhofer Obermair, Christa ^a   Baier, Gottfried ^a  

^a INNSBRUCK MEDICAL UNIVERSITY   (Austria)

^b ST JOSEF HOSPITAL   (Germany)

^c HUMANITAS CLINICAL AND RESEARCH CENTER   (Italy)

Author keywords

Cbl b; SMAD; TGF signaling

Indexed keywords

MESSENGER RNA; SMAD7 PROTEIN; TRANSFORMING GROWTH FACTOR BETA;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CHROMATIN IMMUNOPRECIPITATION; COMPLEX FORMATION; CONTROLLED STUDY; CYTOKINE RESPONSE; DEGRADATION; DNA BINDING; DOWN REGULATION; FEMALE; GENOTYPE; IN VITRO STUDY; IN VIVO STUDY; MOUSE; NONHUMAN; PHENOTYPE; PROTEIN PHOSPHORYLATION; PROTEIN STABILITY; T LYMPHOCYTE; UBIQUITINATION; UPREGULATION;

CBL-B; SMAD; TGFΒ SIGNALING;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; ANIMALS; CELL DIFFERENTIATION; CHROMATIN IMMUNOPRECIPITATION; INTERFERON-GAMMA; MICE; MICE, KNOCKOUT; MICROSCOPY, CONFOCAL; PROTO-ONCOGENE PROTEINS C-CBL; SMAD7 PROTEIN; T-BOX DOMAIN PROTEINS; T-LYMPHOCYTES; TRANSFORMING GROWTH FACTOR BETA; UBIQUITINATION;

EID: 84890413258     PISSN: 16742788     EISSN: 17594685     Source Type: Journal    
DOI: 10.1093/jmcb/mjt017     Document Type: Article

References (58)

1. -/- T cells demonstrate in vivo resistance to regulatory T cells but a context-dependent resistance to TGF-beta. J. Immunol. 185, 2051-2058.
2. Bachmaier, K., Krawczyk, C., Kozieradzki, I., et al. (2000). Negative regulation of lymphocyte activation and autoimmunity by the molecular adaptor Cbl-b. Nature 403, 211-216.
3. Bettelli, E., Carrier, Y., Gao, W., et al. (2006). Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells. Nature 441, 235-238.
4. Bommireddy, R., Saxena, V., Ormsby, I., et al. (2003). TGF-beta 1 regulates lymphocyte homeostasis by preventing activation and subsequent apoptosis of peripheral lymphocytes. J. Immunol. 170, 4612-4622.
5. Carey, M.F., Peterson, C.L., and Smale, S.T. (2009). Chromatin immunoprecipitation (ChIP). Cold Spring Harb. Protoc. 4, pdb.prot5279.
6. Chen, W., and Konkel, J.E. (2010). TGF-βand 'adaptive' Foxp3+regulatory T cells. J. Mol. Cell Biol. 2, 30-36.
7. Chiang, Y.J., Kole, H.K., Brown, K., et al. (2000). Cbl-b regulates the CD28 dependence of T-cell activation. Nature 403, 216-220.
8. Chiang, J.Y., Jang, I.K., Hodes, R., et al. (2007). Ablation of Cbl-b provides protection against transplanted and spontaneous tumors. J. Clin. Invest. 117, 1029-1036.
9. Das, J., Ren, G., Zhang, L., et al. (2009). Transforming growth factor beta is dispensable for the molecular orchestration of Th17 cell differentiation. J. Exp. Med. 206, 2407-2416.
10. Davies, G.C., Ettenberg, S.A., Coats, A.O., et al. (2004). Cbl-b interacts with ubiquitinated proteins; differential functions of the UBA domains of c-Cbl and Cbl-b. Oncogene 23, 7104-7115.
11. - T cells. J. Immunol. 179, 2041-2045.
12. Gorelik, L., and Flavell, R.A. (2000). Abrogation of TGF beta signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease. Immunity 12, 171-181.
13. Gorelik, L., and Flavell, R.A. (2001). Immune-mediated eradication of tumors through the blockade of transforming growth factor-beta signaling in T cells. Nat. Med. 7, 1118-1122.
14. Gorelik, L., Constant, S., and Flavell, R.A. (2002). Mechanism of transforming growth factor beta-induced inhibition of T helper type 1 differentiation. J. Exp. Med. 195, 1499-1505.
15. Govinden, R., and Bhoola, K.D. (2003). Genealogy, expression, and cellular function of transforming growth factor-beta. Pharmacol. Ther. 98, 257-265.
16. Gruber, T., Hermann-Kleiter, N., Hinterleitner, R., et al. (2009). PKC-theta modulates the strength of T cell responses by targeting Cbl-b for ubiquitination and degradation. Sci. Signal. 2, ra30.
17. Harada, Y., Elly, C., Ying, G., et al. (2010). Transcription factors Foxo3a and Foxo1 couple the E3 ligase Cbl-b to the induction of Foxp3 expression in induced regulatory T cells. J. Exp. Med. 207, 1381-1391.
18. Hayashi, H., Abdollah, S., Qiu, Y., et al. (1997). The MAD-related protein Smad7 associates with the TGFbeta receptor and functions as an antagonist of TGFbeta signaling. Cell 89, 1165-1173.
19. Heath, V.L., Murphy, E.E., Crain, C., et al. (2000). TGF-beta1 down-regulates Th2 development and results in decreased IL-4-induced STAT6 activation and GATA-3 expression. Eur. J. Immunol. 30, 2639-2649.
20. Heissmeyer, V., Macian, F., Im, S.H., et al. (2004). Calcineurin imposes T cell unresponsiveness through targeted proteolysis of signaling proteins. Nat. Immunol. 5, 255-265.
21. Ivanov, Ii, Mckenzie, B.S., Zhou, L., et al. (2006). The orphan nuclear receptor ROR gammat directs the differentiation program of proinflammatory IL-17+ T helper cells. Cell 126, 1121-1133.
22. Jeon, M.S., Atfield, A., Venuprasad, K., et al. (2004). Essential role of the E3 ubiquitin ligase Cbl-b in T cell anergy induction. Immunity 21, 167-177.
23. Kavsak, P., Rasmussen, R.K., Causing, C.G., et al. (2000). Smad7 binds to Smurf2 to form an E3 ubiquitin ligase that targets the TGF beta receptor for degradation. Mol. Cell 6, 1365-1375.
24. Kleiter, I., Song, J., Lukas, D., et al. (2010). Smad7 in T cells drives T helper 1 responses in multiple sclerosis and experimental autoimmune encephalomyelitis. Brain 133, 1067-1081.
25. Koinuma, D., Shinozaki, M., Komuro, A., et al. (2003). Arkadia amplifies TGF-beta superfamily signalling through degradation of Smad7. EMBO J. 22, 6458-6470.
26. Krawczyk, C., Bachmaier, K., Sasaki, T., et al. (2000). Cbl-b is a negative regulator of receptor clustering and raft aggregation in T cells. Immunity 13, 463-473.
27. Kumar, S., Naqvi, R.A., Khanna, N., et al. (2011). Disruption of HLA-DR raft, deregulations of Lck-ZAP-70-Cbl-b cross-talk and miR181a towards T cell hyporesponsiveness in leprosy. Mol. Immunol. 48, 1178-1190.
28. + Treg cells induce TGFβ-dependent tolerogenic dendritic cells that suppress the murine lupuslike syndrome. J. Mol. Cell Biol. 4, 409-419.
29. Li, M.O., and Flavell, R.A. (2008). TGF-beta: a master of all T cell trades. Cell 134, 392-404.
30. Li, Q., Lau, A., Morris, T.J., et al. (2004). A syntaxin 1, Galpha(o), and N-type calcium channel complex at a presynaptic nerve terminal: analysis by quantitative immunocolocalization. J. Neurosci. 24, 4070-4081.
31. Li, M.O., Sanjabi, S., and Flavell, R.A. (2006). Transforming growth factor-beta controls development, homeostasis, and tolerance of T cells by regulatory T cell-dependent and-independent mechanisms. Immunity 25, 455-471.
32. Li, Q.J., Chau, J., Ebert, P.J., et al. (2007). miR-181a is an intrinsic modulator of T cell sensitivity and selection. Cell 129, 147-161.
33. + T cells. J. Exp. Med. 204, 879-891.
34. Lucas, P.J., Kim, S.J., Melby, S.J., et al. (2000). Disruption of T cell homeostasis in mice expressing a T cell-specific dominant negative transforming growth factor beta II receptor. J. Exp. Med. 191, 1187-1196.
35. Lutz-Nicoladoni, C., Wallner, S., Stoitzner, P., et al. (2012). Reinforcement of cancer immunotherapy by adoptive transfer of cblb-deficient CD8(+) T cells combined with a DC vaccine. Immunol. Cell Biol. 90, 130-134.
36. Macian, F., Garcia-Cozar, F., Im, S.H., et al. (2002). Transcriptional mechanisms underlying lymphocyte tolerance. Cell 109, 719-731.
37. Massague, J., Seoane, J., and Wotton, D. (2005). Smad transcription factors. Genes Dev. 19, 2783-2810.
38. McKarns, S.C., Schwartz, R.H., and Kaminski, N.E. (2004). Smad3 is essential for TGF-beta 1 to suppress IL-2 production and TCR-induced proliferation, but not IL-2-induced proliferation. J. Immunol. 172, 4275-4284.
39. Nakao, A., Afrakhte, M., Moren, A., et al. (1997). Identification of Smad7, a TGFbeta-inducible antagonist of TGF-beta signalling. Nature 389, 631-635.
40. Naramura, M., Jang, I.K., Kole, H., et al. (2002). c-Cbl and Cbl-b regulate T cell responsiveness by promoting ligand-induced TCR down-modulation. Nat. Immunol. 3, 1192-1199.
41. Paolino, M., Thien, C.B., Gruber, T., et al. (2011). Essential role of E3 ubiquitin ligase activity in Cbl-b-regulated T cell functions. J. Immunol. 186, 2138-2147.
42. Rizzo, A., Waldner, M.J., Stolfi, C., et al. (2011). Smad7 expression in T cells prevents colitis-associated cancer. Cancer Res. 71, 7423-7432.
43. Santarlasci, V., Maggi, L., Capone, M., et al. (2009). TGF-beta indirectly favors the development of human Th17 cells by inhibiting Th1 cells. Eur. J. Immunol. 39, 207-215.
44. Schuster, N., and Krieglstein, K. (2002). Mechanisms of TGF-beta-mediated apoptosis. Cell Tissue Res. 307, 1-14.
45. Shi, W., Sun, C., He, B., et al. (2004). GADD34-PP1c recruited by Smad7 dephosphorylates TGFbeta type I receptor. J. Cell Biol. 164, 291-300.
46. Shull, M.M., Ormsby, I., Kier, A.B., et al. (1992). Targeted disruption of the mouse transforming growth factor-beta 1 gene results in multifocal inflammatory disease. Nature 359, 693-699.
47. Stopa, M., Anhuf, D., Terstegen, L., et al. (2000). Participation of Smad2, Smad3, and Smad4 in transforming growth factor beta (TGF-beta)-induced activation of Smad7. The TGF-beta response element of the promoter requires functional Smad binding element and E-box sequences for transcriptional regulation. J. Biol. Chem. 275, 29308-29317.
48. Takimoto, T., Wakabayashi, Y., Sekiya, T., et al. (2010). Smad2 and Smad3 are redundantly essential for the TGF-beta-mediated regulation of regulatory T plasticity and Th1 development. J. Immunol. 185, 842-855.
49. + T cell-mediated tumor vaccine efficacy by an anti-transforming growth factor-beta monoclonal antibody. Clin. Cancer Res. 15, 6560-6569.
50. Thomas, D.A., and Massague, J. (2005). TGF-beta directly targets cytotoxic T cell functions during tumor evasion of immune surveillance. Cancer Cell 8, 369-380.
51. + regulatory T cells. J. Mol. Cell Biol. 4, 29-37.
52. -/- mice. J. Immunol. 173, 1059-1065.
53. Wohlfert, E.A., Gorelik, L., Mittler, R., et al. (2006). Cutting edge: deficiency in the E3 ubiquitin ligase Cbl-b results in a multifunctional defect in T cell TGF-beta sensitivity in vitro and in vivo. J. Immunol. 176, 1316-1320.
54. Wrana, J.L., Attisano, L., Wieser, R., et al. (1994). Mechanism of activation of the TGF-beta receptor. Nature 370, 341-347.
55. Yamaguchi, T., Kurisaki, A., Yamakawa, N., et al. (2006). FKBP12 functions as an adaptor of the Smad7-Smurf1 complex on activin type I receptor. J. Mol. Endocrinol. 36, 569-579.
56. Zawel, L., Dai, J.L., Buckhaults, P., et al. (1998). Human Smad3 and Smad4 are sequence-specific transcription activators. Mol. Cell 1, 611-617.
57. Zhang, J., Bardos, T., Li, D., et al. (2002). Cutting edge: regulation of T cell activation threshold by CD28 costimulation through targeting Cbl-b for ubiquitination. J. Immunol. 169, 2236-2240.
58. Zhang, S., Fei, T., Zhang, L., et al. (2007). Smad7 antagonizes transforming growth factor beta signaling in the nucleus by interfering with functional Smad-DNA complex formation. Mol. Cell. Biol. 27, 4488-4499.