Regulation of Cellular Antiviral Signaling by Modifications of Ubiquitin and Ubiquitin-like Molecules

The initiation of cellular antiviral signaling depends on host pattern-recognition receptors (PRRs)-mediated recognition of viral nucleic acids that are known as classical pathogen-associated molecular patterns (PAMPs). PRRs recruit adaptor proteins and kinases to activate transcription factors and epigenetic modifiers to regulate transcription of hundreds of genes, the products of which collaborate to elicit antiviral responses. In addition, PRRs-triggered signaling induces activation of various inflammasomes which leads to the release of IL-1β and inflammation. Recent studies have demonstrated that PRRs-triggered signaling is critically regulated by ubiquitin and ubiquitin-like molecules. In this review, we first summarize an updated understanding of cellular antiviral signaling and virus-induced activation of inflammasome and then focus on the regulation of key components by ubiquitin and ubiquitin-like molecules.

Progress in the researches for antitumor NEDD8 activating enzyme inhibitors / 中国药科大学学报

Inhibition of NEDD8 activating enzyme (NAE),the rate limiting enzyme in Neddylation,can suppress the activity of ubiquitin-proteasome system (UPS) pathway and decrease degradations of related proteins,resulting in cell apoptosis.Compared with the proteasome inhibitors,NAE inhibitors can interfere with cellular homeostasis with more specificity.With the rapid development of the research on NAE,a variety of NAE inhibitors have been reported.According to the structure characteristics,NAE inhibitors can be divided into the AMP analogues,double flavonoids deoxidization duckbill alkali ketone derivatives and metal rhodium complex classes,etc.The process of ubiquitinated modified Neddylation,NAE and physiological role of tumor has been introduced in this paper,and the latest progress of NAE inhibitors also has been summarized.

Ubiquitin ligase Smurf1 promotes Smurf2 neddylation modification / 军事医学

Objective To investigate the mechanism of Smad ubiquitination-related factor 2 (Smurf2)neddylation. Methods The Smurf2 protein level was tested by overexpression of Nedd8,while the method of immunoprecipitation(IP) and Western blotting were used to analyz Smurf2-Nedd8 modification.The GST-pulldown experiment was conducted to prove protein interactions.The protein was obtained by grinding mouse tissue and Western blotting was used to test the protein expression level.Results Over expression of Nedd8 could lead to the down regulation of the Smurf2′s protein level.Smurf1 and Smurf2 could interact in the GST-pulldown experiment. Smurf1 could enhance Smurf2-Nedd8 modification.The Smurf2′s protein level was up-regulated in mouse tissue of Smurf1 C426A.Conclusion There is some relationship and also difference between Smurf1 and Smurf2.Smurf1 can enhance Smurf2-Nedd8 modification.

Ubiquitin-like proteins and hepatocellular carcinoma / 中国肿瘤临床

Ubiquitin-like proteins are structurally similar to ubiquitin. These proteins are processed, activated, conjugated, and re-leased from conjugates by enzymatic steps that are similar to the corresponding mechanisms for ubiquitin. Ubiquitin-like proteins regu-late a wide array of cellular processes through modification processes, such as nuclear-cytosolic transport, transcriptional regulation, protein stability, response to stress, and progression through the cell cycle. A large number of recent studies have found dysfunctional ubiquitin-like proteins in hepatocellular carcinoma. These proteins are important in tumorigenesis, cell proliferation, apoptosis, and an-giogenesis. Anticancer drug studies revealed that regulating protein modification by using ubiquitin-like proteins may alter the anti-tu-mor effects of chemotherapy and thus influence the chemosensitivity of hepatocellular carcinoma. Results indicate that ubiquitin-like proteins may become a new target for cancer therapy. The mechanism of ubiquitin-like proteins in tumorigenesis and hepatocellular car-cinoma progression is of great significance in the diagnosis and treatment of hepatocellular carcinoma.

Progress in Function and Regulation of Protein Neddylation / 生物化学与生物物理进展

NEDD8 is a member of the ubiquitin-like proteins. The overall structure of NEDD8 is quite similar to ubiquitin. Covalent conjugation of NEDD8 to proteins at the post-translational level is called Neddylation. Neddylation occurs similarly to ubiquitination and need enzyme cascades involving E1, E2 and E3. Neddylation has been demonstrated to be essential to maintain the ubiquitin ligase activity of Cullin-Roc based E3 ligases. Compared with the ubiquitination which was widely studied in the past two decades, few substrates were identified for Neddylation and the physiological functions of Neddylation need further investigations. The current progress of function and regulation of protein Neddylation will be reviewed.