| First Author | Tripathi BK | Year | 2014 |
| Journal | J Cell Biol | Volume | 207 |
| Issue | 5 | Pages | 627-42 |
| PubMed ID | 25452387 | Mgi Jnum | J:223988 |
| Mgi Id | MGI:5660729 | Doi | 10.1083/jcb.201405105 |
| Citation | Tripathi BK, et al. (2014) CDK5 is a major regulator of the tumor suppressor DLC1. J Cell Biol 207(5):627-42 |
| abstractText | DLC1 is a tumor suppressor protein whose full activity depends on its presence at focal adhesions, its Rho-GTPase activating protein (Rho-GAP) function, and its ability to bind several ligands, including tensin and talin. However, the mechanisms that regulate and coordinate these activities remain poorly understood. Here we identify CDK5, a predominantly cytoplasmic serine/threonine kinase, as an important regulator of DLC1 functions. The CDK5 kinase phosphorylates four serines in DLC1 located N-terminal to the Rho-GAP domain. When not phosphorylated, this N-terminal region functions as an autoinhibitory domain that places DLC1 in a closed, inactive conformation by efficiently binding to the Rho-GAP domain. CDK5 phosphorylation reduces this binding and orchestrates the coordinate activation DLC1, including its localization to focal adhesions, its Rho-GAP activity, and its ability to bind tensin and talin. In cancer, these anti-oncogenic effects of CDK5 can provide selective pressure for the down-regulation of DLC1, which occurs frequently in tumors, and can contribute to the pro-oncogenic activity of CDK5 in lung adenocarcinoma. |
