Modulation of transcriptional corepressor activity of prospero-related homeobox protein (Prox1) by SUMO modification

Abstract 

Prospero-related homeobox protein (Prox1) plays essential roles in the development of many tissues and organs. In the present study, we show that Prox1 is modified by the small ubiquitin-like protein SUMO-1 in cultured cells. Mutation analysis identified at least four potential sumoylation sites within the repression domain of Prox1. Our data indicate that sumoylation of Prox1 reduces its interaction with HDAC3 and as a result downregulates its corepressor activity. These findings suggest that sumoylation may serve as a novel mechanism for the regulation of Prox1’s corepressor activity.

Structured summary

Abbreviations: DBD, DNA binding domain, HDAC, histone deacetylase, LRH-1, liver receptor homologue 1, PIAS, protein inhibitor of activated STAT, Prox1, prospero-related homeobox, SHP, small heterodimer partner, SSP3, SUMO-1 specific peptidase 3, SUMO, small ubiquitin-related modifier

Keywords: Prox1, Sumoylation, HDAC3, Corepressor, Transcription