Schneikert J, Peterziel H, Defossez P A, Klocker H, de Launoit Y, Cato A C
Forschungszentrum Karlsruhe, Institute of Genetics, P.O. Box 3640, D-76021 Karlsruhe, Federal Republic of Germany.
J Biol Chem. 1996 Sep 27;271(39):23907-13. doi: 10.1074/jbc.271.39.23907.
Matrix metalloproteinases belong to a family of structurally related enzymes that plays important role in tissue morphogenesis, differentiation, and wound healing. Their expression is negatively regulated by several members of the steroid hormone receptor family. This is thought to occur through interaction of the steroid receptors with the transcription factor AP-1 that is otherwise required for positive regulation. Here, we demonstrate that AP-1 is not always a target for down-regulation of expression of matrix metalloproteinases by steroid receptors. Androgen receptor negatively regulates matrix metalloproteinase-1 expression not through AP-1 but through a family of Ets-related transcription factors that are also required for positive regulation. This negative regulation is specific for the androgen receptor. It does not require the DNA binding activity but needs amino-terminal sequences of the receptor. These results identify a novel regulatory pathway for negative regulation utilized by a member of the steroid hormone receptor family for down-regulating the expression of matrix metalloproteinases.
基质金属蛋白酶属于一类结构相关的酶家族，在组织形态发生、分化和伤口愈合中发挥重要作用。它们的表达受到类固醇激素受体家族多个成员的负调控。据认为，这是通过类固醇受体与转录因子AP-1的相互作用发生的，而AP-1在正调控中是必需的。在这里，我们证明AP-1并不总是类固醇受体下调基质金属蛋白酶表达的靶点。雄激素受体不是通过AP-1而是通过一类Ets相关转录因子负调控基质金属蛋白酶-1的表达，这些转录因子在正调控中也是必需的。这种负调控对雄激素受体具有特异性。它不需要DNA结合活性，但需要受体的氨基末端序列。这些结果确定了类固醇激素受体家族的一个成员用于下调基质金属蛋白酶表达的负调控的新途径。
