Annexin A1, Annexin A2, and Dyrk 1B are upregulated during GAS1-induced cell cycle arrest

J Cell Physiol. 2018 May;233(5):4166-4182. doi: 10.1002/jcp.26226. Epub 2017 Dec 4.

Abstract

GAS1 is a pleiotropic protein that has been investigated because of its ability to induce cell proliferation, cell arrest, and apoptosis, depending on the cellular or the physiological context in which it is expressed. At this point, we have information about the molecular mechanisms by which GAS1 induces proliferation and apoptosis; but very few studies have been focused on elucidating the mechanisms by which GAS1 induces cell arrest. With the aim of expanding our knowledge on this subject, we first focused our research on finding proteins that were preferentially expressed in cells arrested by serum deprivation. By using a proteomics approach and mass spectrometry analysis, we identified 17 proteins in the 2-DE protein profile of serum deprived NIH3T3 cells. Among them, Annexin A1 (Anxa1), Annexin A2 (Anxa2), dual specificity tyrosine-phosphorylation-regulated kinase 1B (Dyrk1B), and Eukaryotic translation initiation factor 3, F (eIf3f) were upregulated at transcriptional the level in proliferative NIH3T3 cells. Moreover, we demonstrated that Anxa1, Anxa2, and Dyrk1b are upregulated at both the transcriptional and translational levels by the overexpression of GAS1. Thus, our results suggest that the upregulation of Anxa1, Anxa2, and Dyrk1b could be related to the ability of GAS1 to induce cell arrest and maintain cell viability. Finally, we provided further evidence showing that GAS1 through Dyrk 1B leads not only to the arrest of NIH3T3 cells but also maintains cell viability.

Keywords: Annexin A1; Annexin A2; Dyrk 1B; GAS1; cell arrest.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Annexin A1 / genetics*
  • Annexin A2 / genetics*
  • Apoptosis / genetics
  • Cell Cycle Checkpoints / genetics*
  • Cell Cycle Proteins / genetics*
  • Cell Proliferation / genetics
  • Dyrk Kinases
  • Eukaryotic Initiation Factor-3 / genetics
  • GPI-Linked Proteins / genetics
  • Gene Expression Regulation / genetics
  • Humans
  • Mice
  • NIH 3T3 Cells
  • Protein Serine-Threonine Kinases / genetics*
  • Protein-Tyrosine Kinases / genetics*
  • Transcriptional Activation

Substances

  • Annexin A1
  • Annexin A2
  • Cell Cycle Proteins
  • Eukaryotic Initiation Factor-3
  • GPI-Linked Proteins
  • Gas1 protein, mouse
  • annexin A1, mouse
  • Protein-Tyrosine Kinases
  • Protein Serine-Threonine Kinases