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
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
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DOI：
10.1074/jbc.270.43.25715
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发表时间：
1995-10-27
影响因子：
4.8
通讯作者：
RIO, MC
中科院分区：
文献类型：
--
作者：
REGNIER, CH;TOMASETTO, C;RIO, MC
CART 1是一个新的人类基因，它编码的蛋白质具有三个主要的结构域：第一，位于蛋白质氨基端的富含半胱氨酸的结构域，对应于一个不寻常的RING指基序;第二，位于蛋白质核心的原始富含半胱氨酸的结构域，由我们命名为CART基序的HC 3 HC 3共有基序的三个重复序列构成，并且可能与核酸相互作用;第三，CART 1蛋白的羧基末端部分对应于已知参与蛋白质-蛋白质相互作用的TRAF结构域。在人CD 40结合蛋白和小鼠肿瘤坏死因子（TNF）受体相关因子2（TRAF 2）中观察到RING、CART和TRAF结构域的类似关联，两者均参与TNF受体家族介导的信号转导和发育调节的盘基网柄藻DG 17蛋白。CART 1由乳腺癌和转移瘤中的上皮细胞特异性表达。此外，在这些恶性细胞中，CART 1蛋白定位于细胞核中。总之，这些观察结果表明，CART 1可能参与了乳腺癌中TNF相关的细胞因子信号转导。
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.