PTENβ is an alternatively translated isoform of PTEN that regulates rDNA transcription.
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.
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Hui
H
Liang
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Xi
X
Chen
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Qi
Q
Yin
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Danhui
D
Ruan
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Xuyang
X
Zhao
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Cong
C
Zhang
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Michael A
MA
McNutt
Institute of Systems Biomedicine, Department of Pathology, School of Basic Medicine, Beijing Key Laboratory of Tumor Systems Biology, Peking-Tsinghua Center of Life Sciences, Peking University Health Science Center, Beijing 100191, China.
Yuxin
Y
Yin
D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D002466:Cell Nucleolus / Q000235:genetics / Q000378:metabolism; D018387:Codon, Initiator / Q000235:genetics; D004275:DNA, Ribosomal / Q000235:genetics*; D045325:HCT116 Cells; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D008810:Mice, Inbred C57BL; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D014176:Protein Biosynthesis / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D000097796:Nucleolin
D018387:Codon, Initiator; D004275:DNA, Ribosomal; D051059:PTEN Phosphohydrolase; D010750:Phosphoproteins; D020033:Protein Isoforms; D016601:RNA-Binding Proteins; D000097796:Nucleolin