Function and regulation of SUMO proteases

Abstract

Small ubiquitin-related modifier (SUMO) proteases control cellular mechanisms, including transcription, cell division and ribosome biogenesis. The function of SUMO proteases is to remove SUMO from SUMO-modified proteins and (for some SUMO proteases) to process precursor SUMO, which is required for the attachment of SUMO to proteins. Recent studies have characterized two new classes of SUMO proteases. SUMO proteases are now known to fall into one of three distinct classes: the well-characterized UBL-specific protease (Ulp) and sentrin-specific protease (SENP) class; the desumoylating isopeptidase (DESI) class; or the ubiquitin-specific protease-like 1 (USPL1) class. The known SUMO proteases have distinct substrate specificities, which are often largely controlled by the intracellular localization of the enzyme. The non-catalytic, amino-terminal regions of Ulp and SENP enzymes regulate their intracellular localization. High-resolution structures of several SUMO proteases are available, and in some cases the SUMO protease is captured in a covalent, transition state-like complex with SUMO. These structures provide insights into the interactions that occur during SUMO removal from proteins and SUMO processing. The localization, activity or levels of certain SUMO proteases can be modulated by environmental stimuli. For example, certain stimuli cause SENP enzyme levels to change through alterations in the transcription of particular SENP genes. SUMO proteases in yeast and mammals show interesting genetic interactions with a family of enzymes called SUMO-targeted ubiquitin ligases (STUbLs), which add ubiquitin to SUMO-modified proteins. However, many questions remain about the role of SUMO proteases in the pathways that involve STUbLs, particularly the degradation of ubiquitin- and SUMO-modified STUbL substrates by the proteasome.