Presence of a New Conserved Domain in CART1, a Novel Member of the Tumor Necrosis Factor Receptor-associated Protein Family, Which Is Expressed in Breast Carcinoma

Abstract

CART1, a novel human gene, encodes a putative protein exhibiting three main structural domains: first, a cysteine-rich domain located at the amino-terminal part of the protein, which corresponds to an unusual RING finger motif; second, an original cysteine-rich domain located at the core of the protein and constituted by three repeats of an HC3HC3 consensus motif that we designated the CART motif, and which might interact with nucleic acid; third, the carboxyl-terminal part of the CART1 protein corresponds to a TRAF domain known to be involved in protein-protein interactions. Similar association of RING, CART, and TRAF domains was observed in the human CD40-binding protein and in the mouse tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2), both involved in signal transduction mediated by the TNF receptor family and in the developmentally regulated Dictyostelium discoideum DG17 protein. CART1 is specifically expressed by epithelial cells in breast carcinomas and metastases. Moreover, in these malignant cells, the CART1 protein is localized in the nucleus. Altogether, these observations indicate that CART1 may be involved in TNF-related cytokine signal transduction in breast carcinoma.

Expression of the Tumor Necrosis Factor Receptor-Associated Factors (TRAFs) 1 and 2 is a Characteristic Feature of Hodgkin and Reed-Sternberg Cells

“…Interestingly, we found moderate expression of TRAF4 in all three HD cell lines. Before this study, TRAF4 expression was thought to be restricted to breast carcinoma cells and, unlike the other TRAF proteins, was thought to be specifically found in the nucleus (42). The physiologic significance of TRAF4 expression, however, is unknown, and presently, TRAF4 is the only mammalian TRAF that has not been shown to associate with any of the known TNFRs.…”

From receptors to stress-activated MAP kinases

“…The question marks indicate that direct evidence of these pathways remain to be established (TRAF2), which interacts directly with TNFR-2 (Rothe et al, 1994) but is recruited to TNFR-1 via its interaction with TNFR-1-associated death domain protein (TRADD; Hsu et al, 1995Hsu et al, , 1996b. To date, six members of the TRAF family have been identi®ed (Hu et al, 1994;Rothe et al, 1994;Cheng et al, 1995;Mosialos et al, 1995;Re gnier et al, 1995;Cao et al, 1996;Nakano et al, 1996). All TRAFs contain a conserved C-terminal TRAF domain that is used for homo-or hetero-oligomerization and for interaction with the cytoplasmic regions of the TNFR superfamily.…”

“…All TRAFs contain a conserved C-terminal TRAF domain that is used for homo-or hetero-oligomerization and for interaction with the cytoplasmic regions of the TNFR superfamily. With the exception of TRAF1, all TRAF proteins contain an N-terminal Ring ®nger and several zinc ®nger structures that are critical for their e ector functions (Hu et al, 1994;Rothe et al, 1994;Cheng et al, 1995;Mosialos et al, 1995;Re gnier et al, 1995;Cao et al, 1996;Nakano et al, 1996). Structural and biochemical analyses suggest that TRAFs do not possess enzymatic activity, in turn suggesting that they function as adaptor proteins.…”

Severe osteopetrosis, defective interleukin‐1 signalling and lymph node organogenesis in TRAF6‐deficient mice

“…The Epstein-Barr virus protein LMP-1, which was shown to be involved in virus-mediated transformation of B cells, also associates with the TRAF proteins. Six distinct TRAF molecules, TRAF1 to TRAF6, have been identified (Hu et al 1994;Rothe et al 1994;Cheng et al 1995;Mosialos et al 1995;Regnier et al 1995;Sato et al 1995;Cao et al 1996;Ishida et al 1996a;Ishida et al 1996b;Nakano et al 1996). All TRAFs share a common stretch of amino acids at their carboxyl terminus, called the TRAF domain that has been divided into two subregions (Cheng et al 1995).…”