DLC1
Description
The DLC1 (DLC1 Rho GTPase activating protein) is a protein-coding gene located on chromosome 8.
Deleted in Liver Cancer 1 (DLC1), also known as StAR-related lipid transfer protein 12 (STARD12), is a protein encoded by the DLC1 gene. This gene is frequently deleted in various types of solid tumors, including hepatocellular carcinoma, prostate, lung, colorectal, and breast cancers. The DLC1 gene is located on chromosome 8, within a region often deleted in tumors. It is suggested to be a candidate tumor suppressor gene due to its frequent inactivation in cancer cells. The DLC1 protein is localized to focal adhesions and contains four domains: an N-terminal sterile alpha motif (SAM), a serine-rich (SR) region, a Rho-GAP domain, and a C-terminal steroidogenic acute regulatory protein related lipid-transfer (START) domain.
DLC1 functions as a GTPase-activating protein (GAP) for the small GTPases RhoA, RhoB, RhoC and CDC42, terminating their downstream signaling. This induces morphological changes and detachment through cytoskeletal reorganization, playing a critical role in biological processes such as cell migration and proliferation. It also functions in vivo as an activator of the phospholipase PLCD1. Active DLC1 increases cell migration velocity but reduces directionality. DLC1 is required for growth factor-induced epithelial cell migration. In resting cells, DLC1 interacts with TNS3 while PTEN interacts with the p85 regulatory subunit of the PI3K kinase complex. Growth factor stimulation induces phosphorylation of TNS3 and PTEN, causing them to change their binding preference so that PTEN interacts with DLC1 and TNS3 interacts with p85. The PTEN-DLC1 complex translocates to the posterior of migrating cells to activate RhoA, while the TNS3-p85 complex translocates to the leading edge of migrating cells to promote Rac1 activation.
DLC1 is also known as ARHGAP7, HP, STARD12, p122-RhoGAP.
