The lysine-specific demethylase 1 is a novel substrate of protein kinase CK2

Biochim Biophys Acta. 2014 Apr;1844(4):722-9. doi: 10.1016/j.bbapap.2014.01.014. Epub 2014 Jan 31.

Abstract

Protein kinase CK2 is a pleiotropic serine/threonine kinase responsible for the generation of a substantial proportion of the human phosphoproteome. CK2 is generally found as a tetramer with two catalytic, α and α' and two non catalytic β subunits. CK2α C-terminal tail phosphorylation is regulated during the mitotic events and the absence of these phosphosites in α' suggests an isoform specialization. We used a proteomic approach to identify proteins specifically phosphorylated by a CK2α phosphomimetic mutant, CK2αT344ET360ES362ES370E (CK2α4E), in human neuroblastoma SKNBE cellular extract. One of these proteins is lysine-specific demethylase 1 (LSD1 or KDM1A), an important player of the epigenetic machinery. LSD1 is a FAD-dependent amine oxidase and promotes demethylation of lysine 4 and lysine 9 of mono- and di-methylated histone H3. We found that LSD1 is a new substrate and an interacting partner of protein kinase CK2. Three CK2 phosphosites, (Ser131, Ser137 and Ser166) in the N-terminal region of LSD1 have been identified. This domain is found in all chordates but not in more ancient organisms and it is not essential for LSD1 catalytic event while it could modulate the interaction with CK2 and with other partners in gene repressing and activating complexes. Our data support the view that the phosphorylation of the N-terminal domain by CK2 may represent a mechanism for regulating histone methylation, disclosing a new role for protein kinase CK2 in epigenetics.

Keywords: CK2; Demethylation; Epigenetics; LSD1; Phosphorylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Casein Kinase II / genetics
  • Casein Kinase II / metabolism*
  • Cell Line, Tumor
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / metabolism
  • Epigenesis, Genetic*
  • Escherichia coli / genetics
  • Escherichia coli / metabolism
  • Histone Demethylases / genetics
  • Histone Demethylases / metabolism*
  • Histones / genetics
  • Histones / metabolism*
  • Humans
  • Lysine / genetics
  • Lysine / metabolism
  • Methylation
  • Molecular Sequence Data
  • Mutation
  • Neurons / cytology
  • Neurons / metabolism*
  • Phosphorylation
  • Protein Structure, Tertiary
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serine / genetics
  • Serine / metabolism
  • Signal Transduction

Substances

  • Histones
  • Protein Subunits
  • Recombinant Proteins
  • Serine
  • Histone Demethylases
  • KDM1A protein, human
  • Casein Kinase II
  • Lysine