The TRE2 oncoprotein is structurally related to the RabGAP (GTPase-activating protein) family. However, TRE2 seems enzymatically inactive. Two regions are important for its lack of GAP activity. First, the TBC domain, forming the catalytically active domain of RabGAPs, is non-functional in the oncoprotein. Also involved in TRE2 inactivity is the 93-aa region flanking the TBC domain on the C-terminal side. In order to identify the residues responsible for non-functionality, we performed hydrophobic cluster analysis of the oncoprotein sequence, combined with secondary structure prediction, receptor-binding domain analysis, and a tilted peptide calculation. These analyses were complemented with site-directed and random mutagenesis experiments. On the basis of our data, we hypothesize that the lack of secondary structure of the region flanking the TBC domain in TRE2 may explain why this region plays a role in the lack of GAP activity, even when a potentially functional TBC domain is present.
The rapid and large-scale roll-out of new COVID-19 vaccines has led to unprecedented challenges in assessing vaccine safety. In 2021, the European Medicines Agency (EMA) processed about 1.7 million safety reports related to COVID-19 vaccines in the EudraVigilance (EV) database and identified more than 900 potential signals. Beyond the large amount of information to be processed, the evaluation of safety signals has faced several difficulties and limitations, both in the assessment of case reports and in the investigation of databases. The evaluation of a signal of corneal graft rejection (CGR) with Vaxzevria® was no exception to this. In this commentary, we present the challenges encountered in making regulatory decisions in the context of evolving evidence and knowledge. The pandemic crisis emphasised the importance of quick and proactive communication to address the many questions and, above all, to ensure the transparency of safety data.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.