Transcriptional repressor B lymphocyte-induced maturation protein-1 (Blimp-1) is a master regulator of plasma cell differentiation. Here we show that Blimp-1 is covalently modified by SUMO1 at lysine 816, a modification mediated by SUMO E3 ligase PIAS1. Mutation of Blimp-1 lysine 816 reduces transcriptional repression-correlating with a reduced interaction with a histone deacetylase, HDAC2-and impairs differentiation of antibody-secreting cells. Thus, the SUMO pathway critically regulates Blimp-1 function during plasma cell differentiation.
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