Drosophila Bicoid is a substrate of sumoylation and its activator function is subject to inhibition by this post-translational modification.

Bicoid (Bcd) is a Drosophila morphogenetic protein and a transcriptional activator. Genetic studies have suggested a role of sumoylation in Bcd function, but it is unknown how Bcd activity is affected specifically by its own sumoylation status. Here we show that Bcd is sumoylated in Drosophila cells. We identify a lysine residue of Bcd as the primary sumoylation site. Using a Bcd mutant defective in being sumoylated, we show that sumoylation of Bcd is inhibitory to its ability to activate transcription. We provide evidence suggesting that the SUMO moiety has an intrinsic inhibitory activity for the activator function of Bcd.