Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new member of the Cupin superfamily - A possible multifunctional protein acting as an invasion suppressor down-regulated in tumors
Membrane-type 1 matrix metalloproteinase cytoplasmic tail-binding protein-1 is a new member of the Cupin superfamily - A possible multifunctional protein acting as an invasion suppressor down-regulated in tumors
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DOI：
10.1074/jbc.m309957200
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发表时间：
2004-03-26
影响因子：
4.8
通讯作者：
Seiki, M
中科院分区：
文献类型：
--
作者：
Uekita, T;Gotoh, I;Seiki, M
膜型1型基质金属蛋白酶（MT 1 MMP/MMP-14）是一种促进肿瘤细胞在组织中侵袭的酶。虽然MT 1-MMP的蛋白水解活性对于侵袭是不可缺少的，但它也受胞质尾区功能的调节。在这项研究中，我们获得了一个新的人类基因，其产物结合到酵母的尾部序列。该产物MTCBP-1是一种19 kDa的蛋白质，属于新提出的由具有不同功能的蛋白质组成的Cupin超家族。MTCBP-1与MT 1-MMP形成复合物，共定位于细胞膜。在细胞质和细胞核中也检测到MT 1-MMP，其中MT 1-MMP不存在。在人肿瘤细胞系中，MTCBP-1的表达与未转化的成纤维细胞相比显著低，并且MTCBP-1的增强表达抑制了MT 1-MMP促进细胞迁移和侵袭的活性。MTCBP-1与甲硫氨酸代谢中的一种酶--细菌酸还原酮双加氧酶具有显著的同源性。MTCBP-1的C-末端部分与Sip-L相同，据报道Sip-L对人类丙型肝炎病毒复制很重要。因此，MTCBP-1可能具有多种功能，而不是MT 1-MMP的调节，这可能取决于亚细胞区室。
Membrane-type 1 matrix metalloproteinase (MT1MMP/MMP-14) is an enzyme that promotes tumor cell invasion in tissues. Although the proteolytic activity of MT1-MMP is indispensable for invasion, it is also regulated by functions of the cytoplasmic tail. In this study we obtained a new human gene whose product binds to the tail sequence in yeast. The product, MTCBP-1, is a 19-kDa protein that belongs to the newly proposed Cupin superfamily composed of proteins with diverse functions. MTCBP-1 expressed in cells formed a complex with MT1-MMP and co-localized at the membrane. It was also detected in both the cytoplasm and nucleus, where MT1-MMP does not exist. In human tumor cell lines MTCBP-1 expression was significantly low compared with non-transformed fibroblasts, and enforced expression of MTCBP-1 inhibited the activity of MT1-MMP in promoting cell migration and invasion. MTCBP-1 showed significant homology to the bacterial aci-reductone dioxygenase, which is an enzyme in methionine metabolism. The C-terminal part of MTCBP-1 is identical to Sip-L, which is reported to be important for human hepatitis C virus replication. Thus, MTCBP-1 may have multiple functions other than the regulation of MT1-MMP, which presumably depends on the subcellular compartment.