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J. Biol. Chem., Vol. 276, Issue 22, 18649-18652, June 1, 2001

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ACCELERATED PUBLICATION
Pex19p Dampens the p19ARF-p53-p21WAF1 Tumor Suppressor Pathway^*

Takashi Sugihara, Sunil C. Kaul^§, Jun-ya Kato^¶, Roger R. Reddel, Hitoshi Nomura, and Renu Wadhwa^**

From the  Chugai Research Institute for Molecular Medicine, 153-2 Nagai, Niihari-Mura, Ibaraki 300-41, Japan, the ^§ Institute of Molecular and Cell Biology, National Institute of Advanced Industrial Science and Technology (AIST), 1-1 Higashi, Tsukuba, Ibaraki 305-8566, Japan, the ^¶ Graduate School of Biological Sciences, Nara Institute of Science and Technology, 8916-5 Takayama, Ikoma, Nara 630-0101, Japan, and the  Children's Medical Research Institute, Westmead, New South Wales 2145, Australia

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.

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