SUMO proteases: redox regulation and biological consequences.
Small-ubiquitin modifier (SUMO) has emerged as a novel modification system that governs the activities of a wide spectrum of protein substrates. SUMO-specific proteases (SENP) are of particular interest, as they are responsible for both the maturation of SUMO precursors and for their deconjugation. The interruption of SENPs has been implicated in embryonic defects and carcinoma cells, indicating that a proper balance of SUMO conjugation and deconjugation is crucial. Recent advances in molecular and cellular biology have highlighted the distinct subcellular localization, and endopeptidase and isopeptidase activities of SENPs, suggesting that they are nonredundant. A better understanding of the molecular basis of SUMO recognition and hydrolytic cleavage has been obtained from the crystal structures of SENP-substrate complexes. While a number of proteomic studies have shown an upregulation of sumoylation, attention is now increasingly being directed towards the regulatory mechanism of sumoylation, in particular the oxidative effect. Findings on the oxidation-induced intermolecular disulfide of E1-E2 ligases and SENP1/2 have improved our understanding of the mechanism by which modification is switched up or down. More intriguingly, a growing body of evidence suggests that sumoylation cross-talks with other modifications, and that the upstream and downstream signaling pathway is co-regulated by more than one modifier.
Xu
Zheng
Z
Centre for Protein Science and Crystallography, Department of Biochemistry and Molecular Biotechnology Program, Faculty of Science, The Chinese University of Hong Kong, Hong Kong.
Chan
Ho Yin
HY
Lam
Wai Ling
WL
Lam
Kwok Ho
KH
Lam
Levina Suk Mi
LS
Ng
Tzi Bun
TB
Au
Shannon Wing Ngor
SW
D000818:Animals; D010450:Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D010084:Oxidation-Reduction; D015398:Signal Transduction / Q000502:physiology*; D025841:Small Ubiquitin-Related Modifier Proteins / Q000378:metabolism*
D025841:Small Ubiquitin-Related Modifier Proteins; D010450:Endopeptidases