Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5)
Introduction
The tumor necrosis factor (TNF) receptor-associated factor (TRAF) family of proteins is involved in transducing signals from various members of the TNF receptor (TNFR) superfamily (Bazzoni and Beutler, 1995). We have recently cloned cDNAs encoding the mouse TRAF5 protein (mTRAF5) and TRAF6 protein (mTRAF6) via a yeast two-hybrid system using the cytoplasmic domain of CD40 as bait (Ishida et al., 1996a; Ishida et al., 1996b). In vitro binding study revealed that TRAF5 binds to the cytoplasmic domain of CD40, CD30 and lymphotoxin-β receptor (Ishida et al., 1996b; Aizawa et al., 1997; Nakano et al., 1996). Furthermore, TRAF5 lacking a RING finger domain acts as a dominant negative mutant to suppress CD40-mediated induction of CD23 expression in the WEHI231 mouse premature B cell line, suggesting that TRAF5 mediates CD40 signaling (Ishida et al., 1996b). To elucidate the role of TRAF5 in human and compare the structure of mouse and human TRAF5, we have moleculary cloned a cDNA for human TRAF5 and characterized its product.
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Structure of human TRAF5
From 1.2×106 clones of a human Barkitt's lymphoma Daudi cDNA library, nine independent clones were hybridized with 32P-labeled mouse TRAF5 cDNA (Ishida et al., 1996b). Since restriction mapping analysis revealed that clone 5 included the sequences of the other eight clones, cDNA clone 5 was subjected to further analysis. The complete nucleotide sequence has been deposited in the GenBank database (Accession No. AB000509). An open reading frame encoding a predicted protein of 557 aa (calculated
Conclusions
- 1.
A human cDNA encoding the TRAF5 protein was isolated.
- 2.
The human TRAF5 gene is localized on chromosome 1q32.3-q41.1.
- 3.
Human TRAF5 is expressed in various tissues.
- 4.
Human TRAF5 binds more efficiently to the cytoplasmic tail of lymphotoxin-β receptor than to that of CD40 and CD30.
- 5.
Human TRAF5 mediates signal linked to NFκB activation.
Acknowledgements
This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Science, Sports and Culture of Japan, a Grant-in-Aid from the Research Fellowships of the Japan Society for the Promotion of Science for Young Scientists and a Grant-in-Aid for AIDS Research from the Japan Health Sciences Foundation.
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