A novel protein associated with membrane-type 1 matrix metalloproteinase binds p27(kip1) and regulates RhoA activation, actin remodeling, and matrigel invasion.

ABSTRACT: Pericellular proteolysis by membrane-type 1 matrix metalloproteinase (MT1-MMP) plays a pivotal role in tumor cell invasion. Localization of MT1-MMP at the invasion front of cells, e.g. on lamellipodia and invadopodia, has to be regulated in coordination with reorganization of the actin cytoskeleton. However, little is known about how such invasion-related actin structures are regulated at the sites where MT1-MMP localizes. During analysis of MT1-MMP-associated proteins, we identified a heretofore uncharacterized protein. This protein, which we call p27RF-Rho, enhances activation of RhoA by releasing it from inhibition by p27(kip1) and thereby regulates actin structures. p27(kip1) is a well known cell cycle regulator in the nucleus. In contrast, cytoplasmic p27(kip1) has been demonstrated t

SUBMITTER: Hoshino D 

PROVIDER: S-EPMC2785659 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature