Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium

Mol Syst Biol. 2012 Feb 28:8:571. doi: 10.1038/msb.2012.4.


Protein post-translational modifications (PTMs) represent important regulatory states that when combined have been hypothesized to act as molecular codes and to generate a functional diversity beyond genome and transcriptome. We systematically investigate the interplay of protein phosphorylation with other post-transcriptional regulatory mechanisms in the genome-reduced bacterium Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein-specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes. Reciprocally, deletion of the two putative N-acetyltransferases affects protein phosphorylation, confirming cross-talk between the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome revealed that both PTMs are very common, that (as in Eukaryotes) they often co-occur within the same protein and that they are frequently observed at interaction interfaces and in multifunctional proteins. The results imply previously unreported hidden layers of post-transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetylation
  • Acetylesterase / metabolism*
  • Catalytic Domain / genetics
  • Evolution, Molecular
  • Gene Regulatory Networks / genetics
  • Gene Regulatory Networks / physiology
  • Genome Size / genetics*
  • Genome, Bacterial / genetics
  • Lysine / metabolism*
  • Metabolic Networks and Pathways / genetics*
  • Metabolic Networks and Pathways / physiology
  • Models, Biological
  • Organisms, Genetically Modified
  • Phosphorylation / physiology
  • Pneumonia, Mycoplasma / genetics*
  • Pneumonia, Mycoplasma / metabolism
  • Protein Kinases / metabolism*
  • Protein Processing, Post-Translational / genetics
  • Proteome / genetics
  • Proteome / metabolism


  • Proteome
  • Protein Kinases
  • Acetylesterase
  • Lysine