1. Academic Validation
  2. A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF

A novel proapoptotic gene PANO encodes a post-translational modulator of the tumor suppressor p14ARF

  • Exp Cell Res. 2012 Feb 1;318(3):187-95. doi: 10.1016/j.yexcr.2011.10.019.
Akihiro Watari 1 Yang Li Shinji Higashiyama Masuo Yutsudo
Affiliations

Affiliation

  • 1 Cancer Cell Research Group, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
Abstract

The protein p14ARF is a known tumor suppressor protein controlling cell proliferation and survival, which mainly localizes in nucleoli. However, the regulatory mechanisms that govern its activity or expression remain unclear. Here, we report that a novel proapoptotic nucleolar protein, PANO, modulates the expression and activity of p14ARF in HeLa cells. Overexpression of PANO enhances the stability of p14ARF protein by protecting it from degradation, resulting in an increase in p14ARF expression levels. Overexpression of PANO also induces Apoptosis under low serum conditions. This effect is dependent on the nucleolar localization of PANO and inhibited by knocking-down p14ARF. Alternatively, PANO siRNA treated cells exhibit a reduction in p14ARF protein levels. In addition, ectopic expression of PANO suppresses the tumorigenicity of HeLa cells in nude mice. These results indicate that PANO is a new apoptosis-inducing gene by modulating the tumor suppressor protein, p14ARF, and may itself be a new candidate tumor suppressor gene.

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