Phospho-regulated SUMO interaction modules connect the SUMO system to CK2 signaling.
Attachment of SUMO to proteins regulates protein-protein interactions through noncovalent binding of the SUMO moiety to specialized SUMO interaction motifs (SIMs). A core of hydrophobic amino acids has been described as the major determinant of SIM function. Using the transcriptional coregulator and SUMO ligase PIAS1 as a model, we define an extended phospho-regulated SIM module. We show that serine residues adjacent to the hydrophobic core are phosphorylated by CK2 and demonstrate that this dictates binding of free SUMO and SUMO conjugates to PIAS1 in vivo. We provide evidence that the phosphorylated residues contact lysine 39 and 35 in SUMO1 and SUMO2, respectively. Phospho-dependent SUMO binding does not impair the ligase activity but affects the transcriptional coregulatory potential of PIAS1 and other PIAS family members. CK2-regulated phosphoSIM modules were also dissected in the tumor suppressor PML and the exosome component PMSCL1, indicating that these modules serve as general platforms that integrate CK2- and SUMO-regulated signaling networks.
Stehmeier
Per
P
Department of Molecular Cell Biology, Max Planck Institute of Biochemistry, Am Klopferspitz 18, D-82152 Martinsried, Germany.
Muller
Stefan
S
D001665:Binding Sites; D047390:Casein Kinase II / Q000378:metabolism*; D002478:Cells, Cultured; D006367:HeLa Cells; D006801:Humans; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000378:metabolism; D025842:SUMO-1 Protein / Q000378:metabolism*; D015398:Signal Transduction; D014158:Transcription, Genetic; D014162:Transfection
D050828:Protein Inhibitors of Activated STAT; D025842:SUMO-1 Protein; D047390:Casein Kinase II