SATB1 (special AT-rich sequence-binding protein-1) provides a key link between 
DNA loop organization, chromatin modification/remodeling, and association of 
transcription factors at matrix attachment regions (MARs). To investigate the 
role of SATB1 in cellular events, we performed a yeast two-hybrid screen that 
identified SUMO-1, Ubc9, and protein inhibitor of activated STAT (PIAS) family 
members as SATB1 interaction partners. These proteins, working in concert, 
enhanced SUMO conjugation to lysine-744 of SATB1. Overexpression of SUMO or PIAS 
in Jurkat cells, which express high levels of endogenous SATB1, exhibited 
enhanced caspase cleavage of this MAR-associating protein. Sumoylation-deficient 
SATB1 (SATB1(K744R)) failed to display the characteristic caspase cleavage 
pattern; however, fusion of SUMO in-frame to SATB1(K744R) restored cleavage. A 
SUMO-independent interaction of inactive caspase-6 and SATB1 was noted. A subset 
of total cellular SATB1 localized into promyelocytic leukemia nuclear bodies 
where enhanced SATB1 cleavage was detected subsequent to caspase activation. 
These results reveal a novel sumoylation-directed caspase cleavage of this key 
regulatory molecule. The role of regulated proteolysis of SATB1 may be to 
control transcription in immune cells during normal cell functions or to assist 
in efficient and rapid clearance of nonfunctional or potentially damaging immune 
cells.