Proteolytic inactivation of the autoinhibitory prodomain is essential for the pro-tumorigenic function of membrane type-1 matrix metalloproteinase (MT1-MMP)

ABSTRACT: Invasive cancers employ pericellular proteolysis to breach the extracellular matrix and basement membrane barriers and invade the surrounding tissue. Pro-invasive, pro-tumorigenic MT1-MMP is the primary mediator of proteolytic events on the cancer cell surface. Cellular MT1-MMP is synthesized as a latent zymogen. The latency of MT1-MMP is maintained by its N-terminal inhibitory prodomain. Our study reveals a critical mechanism underlying the activation pathway and subsequent execution of the tumor-promoting function of MT1-MMP. Evidence suggests that the prodomain undergoes intradomain cleavage at the PGD↓L50 cleavage site followed by the release of the degraded prodomain by furin cleavage of the R108RKR111↓Y112 site. These events, only if combined, cause the activation of MT1-MMP. The sig

ORGANISM(S): Homo sapiens

SUBMITTER: Andrei Chernov 

PROVIDER: E-GEOD-28655 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress