TY - JOUR
T1 - The ubiquitin-proteasome system is a key component of the SUMO-2/3 cycle
AU - Schimmel, Joost
AU - Larsen, Katja M
AU - Matic, Ivan
AU - van Hagen, Martijn
AU - Cox, Jürgen
AU - Mann, Matthias
AU - Andersen, Jens S
AU - Vertegaal, Alfred C O
PY - 2008
Y1 - 2008
N2 - 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 crosstalk 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. Crosstalk 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 due to 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.
AB - 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 crosstalk 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. Crosstalk 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 due to 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.
U2 - 10.1074/mcp.M800025-MCP200
DO - 10.1074/mcp.M800025-MCP200
M3 - Journal article
C2 - 18565875
SN - 1535-9476
VL - 7
SP - 2107
EP - 2122
JO - Molecular and Cellular Proteomics
JF - Molecular and Cellular Proteomics
IS - 11
ER -