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

Nat Commun. 2017 Mar 23;8:14771. doi: 10.1038/ncomms14771.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing
  • Animals
  • Cell Line, Tumor
  • Cell Nucleolus / genetics
  • Cell Nucleolus / metabolism
  • Codon, Initiator / genetics
  • DNA, Ribosomal / genetics*
  • HCT116 Cells
  • HEK293 Cells
  • HeLa Cells
  • Hep G2 Cells
  • Humans
  • Mice, Inbred C57BL
  • PTEN Phosphohydrolase / genetics*
  • Phosphoproteins / genetics
  • Phosphoproteins / metabolism
  • Phosphorylation
  • Protein Biosynthesis / genetics*
  • Protein Isoforms / genetics
  • RNA-Binding Proteins / genetics
  • RNA-Binding Proteins / metabolism
  • Transcription, Genetic*

Substances

  • Codon, Initiator
  • DNA, Ribosomal
  • Phosphoproteins
  • Protein Isoforms
  • RNA-Binding Proteins
  • nucleolin
  • PTEN Phosphohydrolase