| First Author | Hervy M | Year | 2010 |
| Journal | Genes Cancer | Volume | 1 |
| Issue | 5 | Pages | 506-515 |
| PubMed ID | 20852740 | Mgi Jnum | J:267158 |
| Mgi Id | MGI:6259035 | Doi | 10.1177/1947601910376192 |
| Citation | Hervy M, et al. (2010) The LIM Protein Zyxin Binds CARP-1 and Promotes Apoptosis. Genes Cancer 1(5):506-515 |
| abstractText | Zyxin is a dual-function LIM domain protein that regulates actin dynamics in response to mechanical stress and shuttles between focal adhesions and the cell nucleus. Here we show that zyxin contributes to UV-induced apoptosis. Exposure of wild-type fibroblasts to UV-C irradiation results in apoptotic cell death, whereas cells harboring a homozygous disruption of the zyxin gene display a statistically significant survival advantage. To gain insight into the molecular mechanism by which zyxin promotes apoptotic signaling, we expressed an affinity-tagged zyxin variant in zyxin-null cells and isolated zyxin-associated proteins from cell lysates under physiological conditions. A 130-kDa protein that was co-isolated with zyxin was identified by microsequence analysis as the Cell Cycle and Apoptosis Regulator Protein-1 (CARP-1). CARP-1 associates with the LIM region of zyxin. Zyxin lacking the CARP-1 binding region shows reduced proapoptotic activity in response to UV-C irradiation. We demonstrate that CARP-1 is a nuclear protein. Zyxin is modified by phosphorylation in cells exposed to UV-C irradiation, and nuclear accumulation of zyxin is induced by UV-C exposure. These findings highlight a novel mechanism for modulating the apoptotic response to UV irradiation. |
