Functional interaction of tumor suppressor DLC1 and caveolin-1 in cancer cells.

ABSTRACT: Deleted in liver cancer 1 (DLC1), a tumor suppressor gene frequently inactivated in non-small cell lung cancer (NSCLC) and other malignancies, encodes a multidomain protein with a RhoGTPase-activating (RhoGAP) domain and a StAR-related lipid transfer (START) domain. However, no interacting macromolecule has been mapped to the DLC1 START domain. Caveolin-1 (CAV-1) functions as a tumor suppressor in most contexts and forms a complex with DLC1. Here, we have mapped the region of DLC1 required for interaction with CAV-1 to the DLC1 START domain. Mutation of the DLC1 START domain disrupted the interaction and colocalization with CAV-1. Moreover, DLC1 with a START domain mutation failed to suppress neoplastic growth, although it negatively regulated active Rho. CAV-1 and DLC1 expression levels w

SUBMITTER: Du X 

PROVIDER: S-EPMC6264793 | biostudies-literature | 2012 Sep

REPOSITORIES: biostudies-literature