title: The LIM Protein Zyxin Binds CARP-1 and Promotes Apoptosis.
abstract: 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.
authors.affiliation: Huntsman Cancer Institute, Departments of Biology and Oncological Sciences, University of Utah, Salt Lake City, UT, USA.
authors.forename: Martial
authors.initials: M
authors.lastname: Hervy
authors.forename: Laura M
authors.initials: LM
authors.lastname: Hoffman
authors.forename: Christopher C
authors.initials: CC
authors.lastname: Jensen
authors.forename: Mark
authors.initials: M
authors.lastname: Smith
authors.forename: Mary C
authors.initials: MC
authors.lastname: Beckerle