OTS_1-dependent deSUMOylation increases tolerance to high copper levels in Arabidopsis

The conjugation of SUMO （small ubiquitin-like modifier） to protein substrates is a reversible process （SUMOylation/deSUMOylation） that regulates plant devel- opment and stress responses. The essential metal copper （Cu） is required for normal plant growth, but excess amounts are toxic. The SUMO E3 ligase, SIZI, and SIZ1- mediated SUMOylation function in plant tolerance to excess Cu. It is unknown whether deSUMOylation also contributes to Cu tolerance in plants. Here, we report that OTSI, a protease that cleaves SUMO from its substrate proteins, participates in Cu tolerance in Arabidopsis thaliana （Arabi- dopsis）. OTS1 loss-of-function mutants （otsl-2 and otsl-3） displayed increased sensitivity to excess Cu. Redox homeostasis and the balance between SUMOylation and deSUMOylation were disrupted in the otsl-3 mutant under excess Cu conditions, The otsl-3 mutant accumulated higher levels of Cu in both shoots and roots compared to wild type. Specific Cu-related metal transporter genes were upregu- lated due to the loss-of-function of OTS% which might explain the high Cu levels in otsl-3. These results suggest that the SUMOylation/deSUMOylation machinery is acti- vated in response to excess Cu, and modulates Cu homeostasis and tolerance by regulating both Cu uptake and detoxification. Together, our findings provide insight into the biological function and regulatory role of SUMOylation/deSUMOylation in plant tolerance to Cu.

SENP2 negatively regulates cellular antiviral response by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation

Transcription factor IRF3-mediated type I interferon induction is essential for antiviral innate immunity.We identified the deSUMOylating enzyme Sentrin/SUMO-specific protease(SENP)2 as a negative regulator of virus-triggered IFN-b induction.Overexpression of SENP2 caused IRF3 deSUMOylation,K48-linked ubiquitination,and degradation,whereas depletion of SENP2 had opposite effects.Both the SUMOylation and K48-linked ubiquitination of IRF3 occurred at lysines 70 and 87,and these processes are competitive.The level of virus-triggered IFN-b was markedly up-regulated and viral replication was reduced in SENP2-deficient cells comparing with wild-type controls.Our findings suggest that SENP2 regulates antiviral innate immunity by deSUMOylating IRF3 and conditioning it for ubiquitination and degradation,and provide an example of cross-talk between the ubiquitin and SUMO pathways in innate immunity.

Writing and erasing MYC ubiquitination and SUMOylation

The transcription factor c-MYC(MYC thereafter)controls diverse transcription programs and plays a key role in the development of many human cancers.Cells develop multiple mechanisms to ensure that MYC levels and activity are precisely controlled in normal physiological context.As a short half-lived protein,MYC protein levels are tightly regulated by the ubiquitin proteasome system.Over a dozen of ubiquitin ligases have been found to ubiquitinate MYC whereas a number of deubiquitinating enzymes counteract this process.Recent studies show that SUMOylation and deSUMOylation can also regulate MYC protein stability and activity.Interestingly,evidence suggests an intriguing crosstalk between MYC ubiquitination and SUMOylation.Deregulation of the MYC ubiquitination-SUMOylation regulatory network may contribute to tumorigenesis.This review is intended to provide the current understanding of the complex regulation of the MYC biology by dynamic ubiquitination and SUMOylation and their crosstalk.