PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription

Hui Liang, Xi Chen, Qi Yin, Danhui Ruan, Xuyang Zhao, Cong Zhang, Michael A. McNutt and Yuxin Yin ()
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Hui Liang: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Xi Chen: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Qi Yin: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Danhui Ruan: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Xuyang Zhao: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Cong Zhang: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Michael A. McNutt: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center
Yuxin Yin: Institute of Systems Biomedicine, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTENα, which functions in mitochondrial bioenergetics. Here we report the identification of another N-terminal extended PTEN isoform, designated PTENβ. PTENβ translation is initiated from an AUU codon upstream of and in-frame with the AUG initiation sequence for canonical PTEN. We show that the Kozak context and a downstream hairpin structure are critical for this alternative initiation. PTENβ localizes predominantly in the nucleolus, and physically associates with and dephosphorylates nucleolin, which is a multifunctional nucleolar phosphoprotein. Disruption of PTENβ alters rDNA transcription and promotes ribosomal biogenesis, and this effect can be reversed by re-introduction of PTENβ. Our data show that PTENβ regulates pre-rRNA synthesis and cellular proliferation. These results demonstrate the complexity of the PTEN protein family and the diversity of its functions.

Date: 2017
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DOI: 10.1038/ncomms14771

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