Journal
NATURE COMMUNICATIONS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms14771
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Funding
- National Natural Science Foundation of China [81430056, 31420103905, 81372491]
- National Key Research and Development Program of China [2016YFA0500302]
- Beijing Natural Science Foundation [7161007]
- Lam Chung Nin Foundation for Systems Biomedicine
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PTEN is a critical tumour suppressor that is frequently mutated in human cancer. We have previously identified a CUG initiated PTEN isoform designated PTEN alpha, which functions in mitochondrial bioenergetics. Here we report the identification of another N- terminal extended PTEN isoform, designated PTEN beta. PTENb 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. PTENb localizes predominantly in the nucleolus, and physically associates with and dephosphorylates nucleolin, which is a multifunctional nucleolar phosphoprotein. Disruption of PTENb alters rDNA transcription and promotes ribosomal biogenesis, and this effect can be reversed by re- introduction of PTENb. Our data show that PTENb regulates pre- rRNA synthesis and cellular proliferation. These results demonstrate the complexity of the PTEN protein family and the diversity of its functions.
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