ERM, PEA3 and ETV1 belong to the PEA3 group of ETS transcription factors. They 
are involved in many developmental processes and are transcriptional regulators 
in metastasis. The PEA3 group members share an N-terminal transactivation domain 
(TAD) whose activity is inhibited by a flanking domain named the negative 
regulatory domain (NRD). The mechanism of this inhibition is still unknown. Here 
we show that the NRD maps to residues 73 to 298 in ERM and contains three of the 
five SUMO sites previously identified in the protein. We demonstrate that these 
three SUMO sites are responsible for NRD's inhibitory function in the Gal4 
system. Although the presence of the three sites is required to obtain maximal 
inhibition, only one SUMO site is sufficient to repress transcription whatever 
its localization within the NRD. We also show that NRD is a SUMO-dependent 
repression domain that can act in cis and in trans to downregulate the powerful 
TAD of the VP16 viral protein. In addition, we find that the SUMO sites outside 
the NRD also play a role in the negative regulation of full-length ERM activity. 
We thus postulate that each SUMO site in ERM may function as an inhibitory 
motif.