Elsevier

Gene

Volume 207, Issue 2, 30 January 1998, Pages 135-140
Gene

Cloning and characterization of a cDNA encoding the human homolog of tumor necrosis factor receptor-associated factor 5 (TRAF5)

https://doi.org/10.1016/S0378-1119(97)00616-1Get rights and content

Abstract

A cDNA encoding the human homolog of the tumor necrosis factor receptor-associated factor 5 (TRAF5) protein has been molecularly cloned from a cDNA library of Human Daudi B cell line. The sequence analysis revealed that the cDNA encoded a protein of 557 aa residues with a calculated molecular weight of 64 236. The encoded protein has typical structural characteristics shown in the TRAF family of proteins and binds to the cytoplasmic region of lymphotoxin-β receptor more efficiently than to that of CD40 and CD30. The TRAF5 gene was mapped to the human chromosome 1q32.3-q41.1. Overexpression of human TRAF5 activates NFκB transcription factor in human 293T kidney cells. These results suggest that the human TRAF5 protein could be involved in the signal triggered by various members of the tumor necrosis factor receptor (TNFR) superfamily including CD40, CD30 and lymphotoxin-β receptor.

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.

Section snippets

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.

References (22)

  • I. Berberich et al.

    Crosslinking of CD40 on B cells rapidly activates nuclear factor-κB

    J. Immunol.

    (1994)
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