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

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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)

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.

Suggested Citation

  • Hui Liang & Xi Chen & Qi Yin & Danhui Ruan & Xuyang Zhao & Cong Zhang & Michael A. McNutt & Yuxin Yin, 2017. "PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription," Nature Communications, Nature, vol. 8(1), pages 1-14, April.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_ncomms14771
    DOI: 10.1038/ncomms14771
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    Cited by:

    1. Alla D. Fedorova & Stephen J. Kiniry & Dmitry E. Andreev & Jonathan M. Mudge & Pavel V. Baranov, 2022. "Thousands of human non-AUG extended proteoforms lack evidence of evolutionary selection among mammals," Nature Communications, Nature, vol. 13(1), pages 1-13, December.

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