ABSTRACT
SUMOylation is recently found to function as a targeting signal for the degradation of substrates through the ubiquitin-proteasome system. RNF4 is the most studied human SUMO-targeted ubiquitin E3 ligase. However, the relationship between SUMO proteases, SENPs, and RNF4 remains obscure. There are limited examples of the SENP regulation of SUMO2/3-targeted proteolysis mediated by RNF4. The present study investigated the role of SENP3 in the global protein turnover related to SUMO2/3-targeted ubiquitination and focused in particular on the SENP3 regulation of the stability of Sp1. Our data demonstrated that SENP3 impaired the global ubiquitination profile and promoted the accumulation of many proteins. Sp1, a cancer-associated transcription factor, was among these proteins. SENP3 increased the level of Sp1 protein via antagonizing the SUMO2/3-targeted ubiquitination and the consequent proteasome-dependent degradation that was mediated by RNF4. De-conjugation of SUMO2/3 by SENP3 attenuated the interaction of Sp1 with RNF4. In gastric cancer cell lines and specimens derived from patients and nude mice, the level of Sp1 was generally increased in parallel to the level of SENP3. These results provided a new explanation for the enrichment of the Sp1 protein in various cancers, and revealed a regulation of SUMO2/3 conjugated proteins whose levels may be tightly controlled by SENP3 and RNF4.
Subject(s)
Animals , Humans , Mice , Cysteine Endopeptidases , Genetics , Metabolism , Gene Expression Regulation, Neoplastic , Immunoenzyme Techniques , Immunoprecipitation , Mice, Inbred BALB C , Mice, Nude , Prognosis , Protein Processing, Post-Translational , Proteolysis , RNA, Messenger , Genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Small Ubiquitin-Related Modifier Proteins , Genetics , Metabolism , Sp1 Transcription Factor , Genetics , Metabolism , Stomach Neoplasms , Genetics , Metabolism , Pathology , Sumoylation , Tumor Cells, Cultured , Ubiquitination , Ubiquitins , Genetics , Metabolism , Xenograft Model Antitumor AssaysABSTRACT
Objective To summarize the medical rescue of Chinese Government Medical Team (Chongqing) in Nepal earthquake region in order to explore the work pattern of transnational medical rescue,and improve the rescue efficiency.Methods From the experience about the post-earthquake medical rescue of Chinese Government Medical Team (Chongqing) in Nepal in 2015,several aspects were worthy to summarize such as the establishment of medical team,the layout of camp site,the work algorithm and process,with the analysis of injury feature and outcome of treatment.Results Under the setting of efficient organization and rational assignment of professional work,special working rules,the mutual transfer treatment and multi-disciplinary treatment were employed for 737 emergency patients.Of them,128 patients were hospitalized (including 63 patients completely recovered,56 patients were of clinical improvement,and 9 patients were critically ill transferred to other hospital for advanced treatment),and post-traumatic complication occurred in 48 cases without death.In addition,148 operations were carried out successfully.Conclusions The earthquake disaster has specific feature such as suddenness,a host of casualties and poor rescue conditions,and overseas rescue is with the presence of the language barrier,the difference in living habit,and the lack of coordination with local rescue system,therefore,rationally assigning personnel and resources and establishing work pattern with flexibility,orderly and good communication are the key to promote the efficiency of transnational medical rescue for the injured patients in earthquake region.