3D). Since both K558R and K576R mutants are located in the ligand binding domain and close to the I-box and RXR is not required for repression activity (Fig. 3B and Fig. S6D), we hypothesize that SUMOylation is required for monomerization of Nurr1. Consistent with this, K558R and K576R mutants were less able to activate the NBRE reporter and preferentially activated the DR5 reporter (Fig. S6G). In addition, reconstitution of BV2 microglia cells expressing the Nurr1 shRNA-2 with a non-targeted (NT) form of WT Nurr1 reversed hyperactivation of the endogenous iNOS and TNFα genes, while the non-targeted forms of the SUMOylation mutants (Nurr1 K558R and K576R) did not (Fig. 3E, Fig S6H–I).
