SUMO2 and SUMO3 transcription is differentially regulated by oxidative stress in an Sp1-dependent manner.

Protein SUMOylation (SUMO is small ubiquitin-related modifier) is a dynamic process that is strictly regulated under physiological and pathological conditions. However, little is known about how various intra- or extra-cellular stimuli regulate expression levels of components in the SUMO system. SUMO isoforms SUMO2 and SUMO3 can rapidly convert to be conjugated in response to a variety of cellular stresses. Owing to the limitations of sequence homology, SUMO2 and SUMO3 cannot be differentiated between and are thus referred to as SUMO2/3. Whether these two isoforms are regulated in distinct manners has never been addressed. In the present paper we report that the expression of SUMO3, but not SUMO2, can be down-regulated at the transcription level by cellular oxidative stress. In the present study, we checked SUMO2 and SUMO3 mRNA levels in cells exposed to various doses of H2O2 and in cells bearing different levels of ROS (reactive oxygen species). We found an inverse relationship between SUMO3 transcription and ROS levels. We characterized a promoter region specific for the mouse Sumo3 gene that is bound by the redox-sensitive transcription factor Sp1 (specificity protein 1) and demonstrated oxidation of Sp1, as well as suppression of Sp1-DNA binding upon oxidative stress. This revealed for the first time that the expression of SUMO2 and SUMO3 is regulated differently by ROS. These findings may enhance our understanding about the regulation of SUMOylation and also shed light on the functions of Sp1.

Biochem. J.2011 Apr 15,435(2).

Protein Name:SUMO3
Gene Name:SUMO3 SMT3B SMT3H1

Recombinant Human Small Ubiquitin-Related Modifier 3/SUMO3 produced by our E. coli expression system. The target protein is expressed with sequence (Met1-Phe103) of Human SUMO3 fused with a 6His tag at the N-terminus.

SUMO3 belongs to the SUMO protein family and operates like ubiquitin. Ubiquitin-like protein which can be covalently attached to target lysines either as a monomer or as a lysine-linked polyer. Nevertheless unlike ubiquitin that targets proteins for degration, SUMO3 takes part in several cellular processess, such as nuclear transport, transcription regulation, apoptosis and protein stability. SUMO3 participates in amyloid beta generation and has a key role in the oneset or progression of Alzheimer's disease.