TTRAP explained

Transforming growth factor-β (TGF-β) principally relays its effects through the Smad pathway however, accumulating evidence indicate that alternative signalling routes are also employed by this pleiotropic cytokine. For instance recently, we [?] have demonstrated that ligand-occupied TGF-β receptors can directly trigger the TRAF6-TAK1 signalling module, resulting in MAP kinase activation. Here we report identification of the adaptor molecule TTRAP as a novel component of this non-canonical TGF-β pathway. We show that the protein associates with TGF-β receptors and components of the TRAF6-TAK1 signaling module, resulting in differential regulation of TGF-β activated p38 and NF-κB responses. Modulation of cellular TTRAP level affects cell viability in the presence of TGF-β, suggesting that the protein is an important component of the TGF-β induced apoptotic process.

Interactions

TTRAP has been shown to interact with ETS1,^[1] TNFRSF1B^[2] and CD40.^[2]

Function

This gene encodes a member of a superfamily of divalent cation-dependent phosphodiesterases. The encoded protein associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor associated factors (TRAFs), and inhibits nuclear factor-kappa-B activation. This protein has sequence and structural similarities with APE1 endonuclease, which is involved in both DNA repair and the activation of transcription factors.^[3]

Further reading

• Pype S, Declercq W, Ibrahimi A, Michiels C, Van Rietschoten JG, Dewulf N, de Boer M, Vandenabeele P, Huylebroeck D, Remacle JE . TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation . J. Biol. Chem. . 275 . 24 . 18586–93 . 2000 . 10764746 . 10.1074/jbc.M000531200 . free.
• Hu RM, Han ZG, Song HD, Peng YD, Huang QH, Ren SX, Gu YJ, Huang CH, Li YB, Jiang CL, Fu G, Zhang QH, Gu BW, Dai M, Mao YF, Gao GF, Rong R, Ye M, Zhou J, Xu SH, Gu J, Shi JX, Jin WR, Zhang CK, Wu TM, Huang GY, Chen Z, Chen MD, Chen JL . Gene expression profiling in the human hypothalamus-pituitary-adrenal axis and full-length cDNA cloning . Proc. Natl. Acad. Sci. U.S.A. . 97 . 17 . 9543–8 . 2000 . 10931946 . 16901 . 10.1073/pnas.160270997 . 2000PNAS...97.9543H. free .
• Pei H, Yordy JS, Leng Q, Zhao Q, Watson DK, Li R . EAPII interacts with ETS1 and modulates its transcriptional function . Oncogene . 22 . 18 . 2699–709 . 2003 . 12743594 . 10.1038/sj.onc.1206374 . 35966215 .
• Lee BH, Yoshimatsu K, Maeda A, Ochiai K, Morimatsu M, Araki K, Ogino M, Morikawa S, Arikawa J . Association of the nucleocapsid protein of the Seoul and Hantaan hantaviruses with small ubiquitin-like modifier-1-related molecules . Virus Res. . 98 . 1 . 83–91 . 2003 . 14609633 . 10.1016/j.virusres.2003.09.001.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026.
• Luciano M, Lind PA, Duffy DL, Castles A, Wright MJ, Montgomery GW, Martin NG, Bates TC . A haplotype spanning KIAA0319 and TTRAP is associated with normal variation in reading and spelling ability . Biol. Psychiatry . 62 . 7 . 811–7 . 2007 . 17597587 . 10.1016/j.biopsych.2007.03.007 . 11334660.

Notes and References

1. Pei H, Yordy JS, Leng Q, Zhao Q, Watson DK, Li R . EAPII interacts with ETS1 and modulates its transcriptional function . Oncogene . 22 . 18 . 2699–709 . May 2003 . 12743594 . 10.1038/sj.onc.1206374 . 35966215 .
2. Pype S, Declercq W, Ibrahimi A, Michiels C, Van Rietschoten JG, Dewulf N, de Boer M, Vandenabeele P, Huylebroeck D, Remacle JE . TTRAP, a novel protein that associates with CD40, tumor necrosis factor (TNF) receptor-75 and TNF receptor-associated factors (TRAFs), and that inhibits nuclear factor-kappa B activation . J. Biol. Chem. . 275 . 24 . 18586–93 . June 2000 . 10764746 . 10.1074/jbc.M000531200 . free.
3. Web site: Entrez Gene: TTRAP TRAF and TNF receptor associated protein .