非表示:
キーワード:
Amino Acid Sequence
HeLa Cells
Humans
Leupeptins/pharmacology
Models, Biological
Molecular Sequence Data
Protease Inhibitors/pharmacology
Proteasome Endopeptidase Complex/*metabolism
Proteasome Inhibitors
Protein Processing, Post-Translational
Recombinant Proteins/genetics/metabolism
SUMO-1 Protein/genetics/metabolism
Small Ubiquitin-Related Modifier Proteins/genetics/*metabolism
Ubiquitin/*metabolism
Ubiquitination
Ubiquitins/genetics/*metabolism
要旨:
Many proteins are regulated by a variety of post-translational modifications, and orchestration of these modifications is frequently required for full control of activity. Currently little is known about the combinatorial activity of different post-translational modifications. Here we show that extensive cross-talk exists between sumoylation and ubiquitination. We found that a subset of SUMO-2-conjugated proteins is subsequently ubiquitinated and degraded by the proteasome. In a screen for preferential SUMO-1 or SUMO-2 target proteins, we found that ubiquitin accumulated in purified SUMO-2 conjugates but not in SUMO-1 conjugates. Upon inhibition of the proteasome, the amount of ubiquitin in purified SUMO-2 conjugates increased. In addition, we found that endogenous SUMO-2/3 conjugates, but not endogenous SUMO-1 conjugates, accumulated in response to proteasome inhibitors. Quantitative proteomics experiments enabled the identification of 73 SUMO-2-conjugated proteins that accumulated in cells treated with proteasome inhibitors. Cross-talk between SUMO-2/3 and the ubiquitin-proteasome system controls many target proteins that regulate all aspects of nucleic acid metabolism. Surprisingly the relative abundance of 40 SUMO-2-conjugated proteins was reduced by proteasome inhibitors possibly because of a lack of recycled SUMO-2. We conclude that SUMO-2/3 conjugation and the ubiquitin-proteasome system are tightly integrated and act in a cooperative manner.
