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Identification of STAG1 as a key mediator of a p53-dependent apoptotic pathway

Oncogene volume 23, pages 7621–7627 (2004)Cite this article

Abstract

A mutant version of p53 (p53-121F), in which phenylalanine replaces the 121st serine residue, can induce apoptosis more effectively than wild-type p53 (wt-p53). In view of this observation, we considered that one or more apoptosis-related p53-target genes might be preferentially induced by p53-121F. We carried out cDNA microarray analysis to identify such genes, using mRNAs isolated from LS174T colon-cancer cells infected by adenovirus vectors containing either p53-121F (Ad-p53-121F) or wt-p53 (Ad-p53). The STAG1 gene was one of the transcripts showing higher expression levels in cells infected with Ad-p53-121F as opposed to Ad-wtp53. The encoded product appears to contain a transmembrane domain, and binding motifs for SH3 and WW. In two other cancer cell lines, the expression of STAG1 mRNA was induced in response to various genotoxic stresses in a p53-dependent manner; moreover, enforced expression of STAG1 led to apoptosis in several additional cancer cell lines. Suppression of endogenous STAG1 using the RNA-interference method reduced the apoptotic response, whether induced by Ad-p53-121F or Ad-p53. These results suggest that STAG1, a novel transcriptional target for p53, mediates p53-dependent apoptosis, and might be a good candidate for next-generation gene therapy.

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Acknowledgements

This work was supported in part by Research for the Future Program Grant #00 L 01402 from the Japan Society for the Promotion of Science (YN), and in part by Grants #13216031 and #14028018 from the Ministry of Education, Culture, Sports, Science and Technology (to HA).

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  1. Hirofumi Arakawa

    Present address: Cancer Medicine and Biophysics Division, National Cancer Center Research Institute, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

Authors and Affiliations

  1. Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, 4-6-1, Shirokanedai Minato-ku, Tokyo, 108-8639, Japan

    Yoshio Anazawa, Hirofumi Arakawa, Hidewaki Nakagawa & Yusuke Nakamura

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  1. Yoshio Anazawa
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  2. Hirofumi Arakawa
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Correspondence to Yusuke Nakamura.

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Anazawa, Y., Arakawa, H., Nakagawa, H. et al. Identification of STAG1 as a key mediator of a p53-dependent apoptotic pathway. Oncogene 23, 7621–7627 (2004). https://doi.org/10.1038/sj.onc.1207270

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