| |  |
| |
| Description | Isoform 1: 568 amino acids Isoform 2: 543 amino acids |
| Expression | TRAF3 protein is detected in the skin, with a stronger intensity in more differentiated cells in the upper layers of the complex epithelium. TRAF3 is also expressed in the cartilage, in the cardiovascular system, in the trachea, in the salivary gland, in the liver, in the pancreas, in the prostate gland, in the pituitary gland. A gradient of TRAF3 expression appears to exist along the nephron, with progressively higher expression from proximal tubule to collecting duct. In the central nervous system, many but not most neurons in the cerebral cortex, basal ganglia, and brain stem contain at least low levels of TRAF3 protein. In contrast, almost no expression of TRAF3 is detected in the immune system. |
| Localisation | mainly cytoplasmic |
| Function | The TRAF family proteins act at least in part as adapter proteins that recruit other signaling molecules to ligand-bound TNF family receptors. TRAF3 was first described as a molecule that binds the cytoplasmic tail of CD40. Signaling through CD40 in B cells induces rescue from apoptosis, proliferation, differentiation, Ig production, class switching and expression of co-stimulatory molecules. Insights into the in vivo functions of TRAF3 have come from generation of mice deficient for TRAF3. These mice are depleted in all lineages of peripheral leucocytes, and die shortly after birth. However, B cells from TRAF3-/- upregulate CD23 and proliferate normally in response to CD40 ligand stimulation. Moreover, fetal liver cells from TRAF3 deficient mice can reconstitute the immune system of irradiated wild type mice, although isotype switching in response to T-dependent antigens is defective. Thus, TRAF3 is not required for CD40 signaling, but appears important in T cell-dependent immune responses. These effects of TRAF3 may be mediated through other TNF receptor family members : TRAF3 can bind directly to the cytosolic domains of CD27, CD30, LTbR, LMP-1, and also binds indirectly TNF-R2. |
| Homology | TRAF3 belongs to a family of six proteins (TRAF1 to 6), sharing a common structural organization. TRAF3 counterparts are found in mouse, fly and worm. |
| Involvement of CRAF1, a relative of TRAF, in CD40 signaling. |
| Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D |
| Science (New York, N.Y.). 1995 ; 267 (5203) : 1494-1498. |
| PMID 7533327 |
| |
| Targeted disruption of TRAF3 leads to postnatal lethality and defective T-dependent immune responses. |
| Xu Y, Cheng G, Baltimore D |
| Immunity. 1996 ; 5 (5) : 407-415. |
| PMID 8934568 |
| |
| Immunohistochemical analysis of in vivo patterns of TRAF-3 expression, a member of the TNF receptor-associated factor family. |
| Krajewski S, Zapata JM, Krajewska M, VanArsdale T, Shabaik A, Gascoyne RD, Reed JC |
| Journal of immunology (Baltimore, Md. : 1950). 1997 ; 159 (12) : 5841-5852. |
| PMID 9550380 |
| |
| A single gene for human TRAF-3 at chromosome 14q32.3 encodes a variety of mRNA species by alternative polyadenylation, mRNA splicing and transcription initiation. |
| van Eyndhoven WG, Frank D, Kalachikov S, Cleary AM, Hong DI, Cho E, Nasr S, Perez AJ, Mackus WJ, Cayanis E, Wellington S, Fischer SG, Warburton D, Lederman S |
| Molecular immunology. 1998 ; 35 (18) : 1189-1206. |
| PMID 10199393 |
| |
| Epstein-Barr virus and a cellular signaling pathway in lymphomas from immunosuppressed patients. |
| Liebowitz D |
| The New England journal of medicine. 1998 ; 338 (20) : 1413-1421. |
| PMID 9580648 |
| |
| Hodgkin disease: pharmacologic intervention of the CD40-NF kappa B pathway by a protease inhibitor. |
| Annunziata CM, Safiran YJ, Irving SG, Kasid UN, Cossman J |
| Blood. 2000 ; 96 (8) : 2841-2848. |
| PMID 11023520 |
| |
| Membrane localization of TRAF 3 enables JNK activation. |
| Dadgostar H, Cheng G |
| The Journal of biological chemistry. 2000 ; 275 (4) : 2539-2544. |
| PMID 10644711 |
| |
| Tumor necrosis factor receptor-associated factors (TRAFs). |
| Bradley JR, Pober JS |
| Oncogene. 2001 ; 20 (44) : 6482-6491. |
| PMID 11607847 |
| |