Abstract:

SUMO, an ubiquitin-like protein, can covalently conjugate proteins and plays a role in the regulation of target protein functions and localizations. Similar to ubiquitin, SUMO modification is a dynamic process catalyzed by E1, E2, and E3 and reversed by Sentrin/SUMO-specific proteases (SENPs). To date, 6 SENP members have been defined in human cells, each of which has different cell localization and target specificity. However, the physiologic functions of SENPs are not fully understood. By analysis of SENPs knock-out mice, we find that SENP1 regulates hypoxia-HIF1α signaling or androgen receptor (AR) signaling through positive feedback loop, and plays an important role in HIF1α or AR-involved physiologic and pathologic processes. We also find that SENP2 is essential for suppression of polycomb group protein-mediated gene silencing during heart development. These results reveal the critical roles of SENPs in the regulation of targets-involved signaling.

Key words: small ubiquitin-related modifier protein, protein modification, Sentrin/SUMO-specific protease