Intradomain cleavage of inhibitory prodomain is essential to protumorigenic function of membrane type-1 matrix metalloproteinase (MT1-MMP) in vivo.

ABSTRACT: Invasive cancers use pericellular proteolysis to breach the extracellular matrix and basement membrane barriers and invade the surrounding tissue. Proinvasive membrane type-1 matrix metalloproteinase (MT1-MMP) is the primary mediator of proteolytic events on the cancer cell surface. MT1-MMP is synthesized as a zymogen. The latency of MT1-MMP is maintained by its N-terminal inhibitory prodomain. In the course of MT1-MMP activation, the R(108)RKR(111) ↓ Y(112) prodomain sequence is processed by furin. The intact prodomain released by furin alone, however, is a potent inhibitor of the emerging MT1-MMP enzyme. Evidence suggests that the prodomain undergoes intradomain cleavage at the PGD ↓ L(50) site followed by the release of the degraded prodomain by furin cleavage that finalizes the two-ste

SUBMITTER: Golubkov VS 

PROVIDER: S-EPMC3190797 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature