SUMOylation of Myc-family proteins

PLoS One. 2014 Mar 7;9(3):e91072. doi: 10.1371/journal.pone.0091072. eCollection 2014.

Abstract

Myc-family proteins are key controllers of the metabolic and proliferative status of the cell, and are subjected to a complex network of regulatory events that guarantee their efficient and fast modulation by extracellular stimuli. Hence, unbalances in regulatory mechanisms leading to altered Myc levels or activities are often reported in cancer cells. Here we show that c- and N-Myc are conjugated to SUMO proteins at conserved lysines in their C-terminal domain. No obvious effects of SUMOylation were detected on bulk N-Myc stability or activities, including the regulation of transcription, proliferation or apoptosis. N-Myc SUMOylation could be induced by cellular stresses, such as heat shock and proteasome inhibition, and in all instances concerned a small fraction of the N-Myc protein. We surmise that, as shown for other substrates, SUMOylation may be part of a quality-control mechanism acting on misfolded Myc proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line, Tumor
  • Heat-Shock Response
  • Humans
  • Lysine / metabolism
  • Mice
  • Molecular Sequence Data
  • Mutant Proteins / metabolism
  • Proto-Oncogene Proteins c-myc / chemistry
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Small Ubiquitin-Related Modifier Proteins / metabolism
  • Stress, Physiological
  • Sumoylation*

Substances

  • Mutant Proteins
  • Proto-Oncogene Proteins c-myc
  • Small Ubiquitin-Related Modifier Proteins
  • Lysine

Grants and funding

Work was supported by grants from the EU-FP7 Program (EuroSystem), the European Research Council, the Italian health ministry and the Italian Association for Cancer Research (AIRC). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.