14-3-3 proteins tune non-muscle myosin II assembly

J Biol Chem. 2018 May 4;293(18):6751-6761. doi: 10.1074/jbc.M117.819391. Epub 2018 Mar 16.


The 14-3-3 family comprises a group of small proteins that are essential, ubiquitous, and highly conserved across eukaryotes. Overexpression of the 14-3-3 proteins σ, ϵ, ζ, and η correlates with high metastatic potential in multiple cancer types. In Dictyostelium, 14-3-3 promotes myosin II turnover in the cell cortex and modulates cortical tension, cell shape, and cytokinesis. In light of the important roles of 14-3-3 proteins across a broad range of eukaryotic species, we sought to determine how 14-3-3 proteins interact with myosin II. Here, conducting in vitro and in vivo studies of both Dictyostelium (one 14-3-3 and one myosin II) and human proteins (seven 14-3-3s and three nonmuscle myosin IIs), we investigated the mechanism by which 14-3-3 proteins regulate myosin II assembly. Using in vitro assembly assays with purified myosin II tail fragments and 14-3-3, we demonstrate that this interaction is direct and phosphorylation-independent. All seven human 14-3-3 proteins also altered assembly of at least one paralog of myosin II. Our findings indicate a mechanism of myosin II assembly regulation that is mechanistically conserved across a billion years of evolution from amebas to humans. We predict that altered 14-3-3 expression in humans inhibits the tumor suppressor myosin II, contributing to the changes in cell mechanics observed in many metastatic cancers.

Keywords: 14-3-3 protein; Dictyostelium; bipolar filament assembly; cytoskeleton; fluorescence correlation spectroscopy (FCS); human; myosin; surface plasmon resonance (SPR).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism*
  • 14-3-3 Proteins / physiology
  • Animals
  • Chromatography, Gel
  • Cytokinesis / physiology
  • Dictyostelium / metabolism
  • Humans
  • Myosin Type II / metabolism*
  • Phosphorylation
  • Protein Binding
  • Protozoan Proteins / metabolism
  • Spectrometry, Fluorescence
  • Surface Plasmon Resonance


  • 14-3-3 Proteins
  • Protozoan Proteins
  • Myosin Type II