title: A PTEN translational isoform has PTEN-like activity.
abstract: BACKGROUND
  To identify PTEN isoform and explore its potential role in tumor suppression.
  
  
  METHODS
  Western blotting, over-expression, shRNA mediated knocking-down, and bioinformatic analysis were used to identify PTEN isoform and test its effect on PI3K-Akt signaling pathway. Cell proliferation, apoptosis, and migration assays were used to test PTEN isoform's biological activities.
  
  
  RESULTS
  The PTEN isoform is about 15 kDa bigger than PTEN and its expression is dependent on PTEN status. Immunoprecipitation for PTEN isoform followed by screening with antibodies against ISG15, SUMO1/2/3, Ubiquitin, and Nedd8 showed the identified PTEN isoform is not a general proteinaceous post-translational modification. In addition, overexpression of PTEN cDNA in cells did not generate PTEN isoform whereas knocking-down of PTEN reduced the protein levels of both PTEN and PTEN isoform in a proportional manner. Analysis of PTEN DNA sequence disclosed an alternative translational starting code (CTG) upstream of canonical PTEN coding sequence. Expression of cloned PTEN isoform generated a protein with a size about 15 kDa bigger than PTEN and suppressed PI3K-Akt signaling pathway in cells. Overexpression of PTEN isoform also led to decrease in cell growth and enhanced serum starvation-and UV irradiation-induced apoptosis through activation of Caspase 3. Finally, expression of PTEN isoform inhibited cell migration in scratch assay.
  
  
  CONCLUSIONS
  PTEN isoform has PTEN-like activity and might be a new tumor suppressor.
authors.affiliation: 1 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Xie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: 1 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Bowei
authors.initials: B
authors.lastname: Yin
authors.affiliation: 1 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Zhu
authors.affiliation: 1 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Guochang
authors.initials: G
authors.lastname: Huang
authors.affiliation: 1 Department of Gastroenterology, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang, China ; 2 School of Medicine, Ningbo University, Ningbo 315211, Zhejiang, China ; 3 Ningbo Medical Center, 4 Minimally Invasive Abdominal Surgery, Ningbo Medical Center, LiHuiLi Hospital, Ningbo 315040, Zhejiang Province, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
keywords: PI3K-Akt; PTEN; PTEN isoform; apoptosis; cell growth; cell migration; tumor suppressor