Jade-1S phosphorylation induced by CK1α contributes to cell cycle progression

Cell Cycle. 2016;15(8):1034-45. doi: 10.1080/15384101.2016.1152429.


The PHD zinc finger protein Jade-1S is a component of the HBO1 histone acetyltransferase complex and binds chromatin in a cell cycle-dependent manner. Jade-1S also acts as an E3 ubiquitin ligase for the canonical Wnt effector protein β-catenin and is influenced by CK1α-mediated phosphorylation. To further elucidate the functional impact of this phosphorylation, we used a stable, low-level expression system to express either wild-type or mutant Jade-1S lacking the N-terminal CK1α phosphorylation motif. Interactome analyses revealed that the Jade-1S mutant unable to be phosphorylated by CK1α has an increased binding affinity to proteins involved in chromatin remodelling, histone deacetylation, transcriptional repression, and ribosome biogenesis. Interestingly, cells expressing the mutant displayed an elongated cell shape and a delay in cell cycle progression. Finally, phosphoproteomic analyses allowed identification of a Jade-1S site phosphorylated in the presence of CK1α but closely resembling a PLK1 phosphorylation motif. Our data suggest that Jade-1S phosphorylation at an N-terminal CK1α motif creates a PLK1 phospho-binding domain. We propose CK1α phosphorylation of Jade 1S to serve as a molecular switch, turning off chromatin remodelling functions of Jade-1S and allowing timely cell cycle progression. As Jade-1S protein expression in the kidney is altered upon renal injury, this could contribute to understanding mechanisms underlying epithelial injury repair.

Keywords: CK1α; Cell cycle; Jade-1S; NuRD complex; PLK1; S-phase; mitosis; proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Casein Kinase Ialpha / metabolism*
  • Cell Cycle Proteins / metabolism
  • Cell Cycle*
  • Cell Proliferation
  • DNA Nucleotidyltransferases / metabolism
  • Green Fluorescent Proteins / metabolism
  • HEK293 Cells
  • Homeodomain Proteins / metabolism*
  • Humans
  • Mice
  • Mutation
  • NIH 3T3 Cells
  • Phosphorylation
  • Phosphoserine / metabolism
  • Protein Interaction Mapping
  • Protein Serine-Threonine Kinases / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Tumor Suppressor Proteins / metabolism*


  • Cell Cycle Proteins
  • Homeodomain Proteins
  • JADE1 protein, human
  • Jade1 protein, mouse
  • Proto-Oncogene Proteins
  • Tumor Suppressor Proteins
  • Green Fluorescent Proteins
  • Phosphoserine
  • Casein Kinase Ialpha
  • Protein Serine-Threonine Kinases
  • polo-like kinase 1
  • DNA Nucleotidyltransferases
  • FLP recombinase