ISPT organization

Research
The laboratory is interested in understanding the functions and mechanisms of ubiquitin (Ub)-dependent or autophagic proteolysis, with an emphasis on the N-degron pathway. In normal conditions, the Nt-Arg of arginylated substrates is recognized by the UBR box of UBR proteins for degradation through the UPS. However, if proteolytic flux via the UPS is compromised, the Nt-Arg of the substrates is preferentially recognized by the ZZ domain of p62, facilitating p62 self-polymerization, autophagosome biogenesis, and lysosomal degradation of autophagic protein cargoes. Moreover, with roles of N-terminal arginine in autophagy, the N-degron pathway mediates the selective autophagy like reticulophagy, pexophagy, lipophagy, and xenophagy. With these principles, N-terminal arginine mimic chemicals can facilitate degradation of misfolded proteins via mediating UPS or autophagy. With principles that N-terminal arginine mimic chemicals bind to and activate p62 and autophagy, our lab studied about targeted degradation.

Research
Molecular and functional analysis of protein recognition and degradation in plant.
We have developed a transgenic in vivo protein stability reporter system as a molecular tool that allows screening for mutants defective in PQC and combine genetics, cell biology and state-of-the-art biochemistry. A long-term goal is to understand the biological significance of plant PQC in the context of development and biotechnology by elucidating protein quality checkpoints and proteostatic control in general, but also focused on plant yield and stress signalling.

NERD – the N-end rule pathway of targeted protein degradation
Our laboratory work is mainly focused on genetical and protein biochemical studies of enzymatic NERD components (E3 Ubiquitin ligases, arginyl-transferases, and amidases), their substrate proteins as well as biotechnological applications of NERD in plants. Moreover, we have successfully implemented a temperature-dependent protein accumulation technique in plants which relies on protein stability modulated by NERD. By using this technique, we can accumulate or deplete a specific artificial target protein fusion in living plants

Research
Most proteins are chemically modified in the cell and such modifications are often crucial for the protein’s ability to carry out its function. N-terminal acetylation is one of the most common protein modifications in eukaryotes. It is catalyzed by N-terminal acetyltransferases (NATs) which are linked to cancer, genetic syndromes, and regulation of human metabolism. The focus of our lab is the molecular biology of protein N-terminal acetylation and NATs. We are using various eukaryotic model systems such as the budding yeast Saccharomyces cerevisiae, the nematode Caenorhabditis elegans, mammalian cell lines and zebrafish (Danio rerio), combined with in vitro approaches.

Research
Our team focuses on elucidating the fundamental mechanism, role, and impact on protein fate of essential N-terminal co-translational modifications that affect most prokaryotic and eukaryotic proteins (Fig. 1). Our team develops parallel activities on therapeutic applications.
The group uses an integrated strategy, involving reverse and chemical genomics applied to various organisms, ranging from targeted structural and cellular biochemistry analysis to proteomics and bioinformatics approaches. We also develop and make available tools and resources.

Research
My research work in recent years has focused on understand the importance of oxygen sensing in plants, and discovering the roles that the N-degron pathways of ubiquitin-mediated proteolysis play in regulating plant development and responses to the environment (recent review here). We showed that the pathway controls development, response to multiple abiotic and biotic stresses, and that oxygen-sensing through this pathway is a component of skotomorphogenesis, mitochondrial retrograde signaling, geographical adaptation to humidity, and adaptation to absolute altitude.

Research
We first discovered that N-terminal acetylation acts as a proteolytic signal that causes proteolysis, and we found a clue to solve this mystery. Furthermore, the associated acetylated N-terminal rule pathway was first identified. In addition, the N-terminal methionine proteolysis signal, which holds the 'fate of intracellular proteins', was first identified. In recent years, unlike previous theories, the eukaryotic cytoplasm can start protein synthesis from formula methionine, which is recognized and processed as a proteolytic signal. This discovery not only presented a new paradigm for protein synthesis, degradation, and mitochondrial resonance, but also opened up a whole new area of research.

Research
The goal of our research is to investigate the physiological role of a previously uncharacterized posttranslational modification, protein arginylation. Our current studies are focused on three major directions: (1) identification of the ATE1 protein targets and studying the effect of arginylation on their properties and functions; (2) studies of the structure and molecular properties of the mouse ATE1 enzymes; and (3) discovering the mechanisms and pathways that lead to the global physiological effects of protein arginylation.