Sec6 regulated cytoplasmic translocation and degradation of p27 via interactions with Jab1 and Siah1

Cell Signal. 2014 Oct;26(10):2071-85. doi: 10.1016/j.cellsig.2014.06.003. Epub 2014 Jun 18.

Abstract

p27 has essential roles in cellular proliferation and migration, and reduced or cytoplasmic p27 is associated with poor clinical outcomes in a variety of human tumours. Jun activation domain-binding protein (Jab1)/constitutive photomorphogenic-9 signalosome 5 (CSN5) directly interacts with p27 promoting its translocation and cytoplasmic degradation. Sec6 is a component of the exocyst complex. Recently, several studies revealed that Sec6 has specific functions in migration, adhesion, and cell differentiation. However, how Sec6 is involved in the regulation of cell cycle progression is unknown. The present study shows that Sec6 regulates cytoplasmic translocation of p27 through p27 phosphorylation at Thr157, thereby promoting p27 degradation in the cytoplasm via interaction with Jab1 and Siah1 and suppressing cell cycle progression.

Keywords: Cell cycle arrest; Jun activation domain-binding protein 1; Sec6; Seven in absentia homolog 1; p27.

MeSH terms

  • 14-3-3 Proteins / chemistry
  • 14-3-3 Proteins / metabolism
  • COP9 Signalosome Complex
  • Cell Cycle Checkpoints
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cyclin-Dependent Kinase Inhibitor p27 / chemistry
  • Cyclin-Dependent Kinase Inhibitor p27 / metabolism*
  • Cytoplasm / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells
  • Humans
  • Immunoprecipitation
  • Intracellular Signaling Peptides and Proteins / antagonists & inhibitors
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Nuclear Proteins / chemistry
  • Nuclear Proteins / metabolism*
  • Peptide Hydrolases / genetics
  • Peptide Hydrolases / metabolism*
  • Phosphorylation
  • Protein Binding
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Translocation, Genetic
  • Ubiquitin-Protein Ligases / chemistry
  • Ubiquitin-Protein Ligases / metabolism*
  • Vesicular Transport Proteins / antagonists & inhibitors
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*

Substances

  • 14-3-3 Proteins
  • EXOC3 protein, human
  • EXOC4 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Nuclear Proteins
  • RNA, Small Interfering
  • Vesicular Transport Proteins
  • Cyclin-Dependent Kinase Inhibitor p27
  • Ubiquitin-Protein Ligases
  • seven in absentia proteins
  • Peptide Hydrolases
  • COPS5 protein, human
  • COP9 Signalosome Complex