RSUME, a small RWD-containing protein, enhances SUMO conjugation and stabilizes HIF-1 during hypoxia

CARBIA NAGASHIMA A, GEREZ, J, PEREZ CASTRO C, PAEZ PEREDA MP, SILBERSTEIN, S., STALLA GK, HOLSBOER, F, ARZT E.

Cell

Año: 2007 vol. 131 p. 309 - 323

SUMO conjugation to proteins is involved in the regulation of diverse cellular functions. We haveidentified a protein, RWD-containing sumoylation enhancer (RSUME), that enhances overallSUMO-1, -2, and -3 conjugation by interacting with the SUMO conjugase Ubc9. RSUME increases noncovalent binding of SUMO-1 to Ubc9 and enhances Ubc9 thioester formation and SUMO polymerization. RSUME enhances the sumoylation of IkB in vitro and in culturedcells, leading to an inhibition of NF-kB transcriptional activity. RSUME is induced by hypoxia and enhances the sumoylation of HIF-1a, promoting its stabilization and transcriptionalactivity during hypoxia. Disruption of the RWD domain structure of RSUME demonstrates thatthis domain is critical for RSUME action. Together, these findings point to a central role ofRSUME in the regulation of sumoylation and, hence, several critical regulatory pathways in mammalian cells.