Phosphorylation-dependent interaction of SATB1 and PIAS1 directs SUMO-regulated caspase cleavage of SATB1.
Special AT-rich sequence-binding protein 1 (SATB1) is a tissue-restricted genome organizer that provides a key link between DNA loop organization, chromatin modification/remodeling, and transcription factor association at matrix attachment regions (MARs). The SUMO E3 ligase PIAS1 enhances SUMO conjugation to SATB1 lysine-744, and this modification regulates caspase-6 mediated cleavage of SATB1 at promyelocytic leukemia nuclear bodies (PML NBs). Since this regulated caspase cleavage occurs on only a subset of SATB1, and the products are relatively stable, proteolysis likely mediates cellular processes other than programmed cell death. However, the mechanism for the spatial and temporal regulation of SATB1 sumoylation and caspase cleavage is not known. Here we report that these processes are controlled by SATB1 phosphorylation; specifically, PIAS1 interaction with SATB1 is inhibited by phosphorylation. Mutagenesis studies identified interaction of the PIAS SAP (scaffold attachment factor-A/B/acinus/PIAS) motif with SATB1 N-terminal sequences. Notably, phosphorylation of SATB1 at threonine-188 regulates its interaction with PIAS1. Sequences near this phosphorylation site, LXXLL (residues 193 to 197), appear to be conserved among a subset of SUMO substrate proteins. Thus, this motif may be commonly involved in interaction with the PIAS SAP, and phosphorylation may similarly inhibit some of these substrates by preventing their interaction with the ligase.
Tan
Joseph-Anthony T
JA
Division of Molecular Medicine, Beckman Research Institute, City of Hope, 1500 E. Duarte Rd., Duarte, CA 91010, USA.
Song
Jing
J
Chen
Yuan
Y
Durrin
Linda K
LK
D000595:Amino Acid Sequence; D000818:Animals; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D006801:Humans; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010766:Phosphorylation; D050828:Protein Inhibitors of Activated STAT / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment; D025841:Small Ubiquitin-Related Modifier Proteins / Q000235:genetics / Q000378:metabolism*; D020798:Two-Hybrid System Techniques
D036961:Matrix Attachment Region Binding Proteins; D050828:Protein Inhibitors of Activated STAT; D011993:Recombinant Fusion Proteins; C076189:SATB1 protein, human; D025841:Small Ubiquitin-Related Modifier Proteins; D020169:Caspases