Sugihara T, Kaul S C, Kato J, Reddel R R, Nomura H, Wadhwa R
Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari-Mura, Ibaraki 300-41, Japan.
J Biol Chem. 2001 Jun 1;276(22):18649-52. doi: 10.1074/jbc.C100011200. Epub 2001 Mar 19.
We isolated a 33-kDa protein, Pex19p/HK33/HsPXF, as a p19ARF-binding protein in a yeast two-hybrid screen. We demonstrate here that Pex19p interacts with p19ARF in the cell cytoplasm and excludes p19ARF from the nucleus, leading to a concurrent inactivation of p53 function. Down-regulation of Pex19p by its antisense expression resulted in increased levels of p19ARF, increased p53 function, and a p53/p21WAF1-mediated senescence-like cell cycle arrest. The data demonstrated a novel mechanism of down-regulation of the p19ARF-p53 pathway.
在酵母双杂交筛选中，我们分离出一种33 kDa的蛋白质Pex19p/HK33/HsPXF，作为一种p19ARF结合蛋白。我们在此证明，Pex19p在细胞质中与p19ARF相互作用，并将p19ARF排除在细胞核外，从而导致p53功能同时失活。通过反义表达下调Pex19p可导致p19ARF水平升高、p53功能增强以及p53/p21WAF1介导的衰老样细胞周期停滞。这些数据证明了一种新的p19ARF-p53途径下调机制。
