Modifications post-traductionnelles d'une serpine humaine recombinante exprimée chez les plantes

Tableau d’honneur de la Faculté des études supérieures et postdoctorales, 2007-2008

Modifications post-traductionnelles d une serpine humaine recombinante exprimée chez les plantes

ROUEN-BU Sciences (764512102) / SudocSudocFranceF

Protein modifications in the plant secretory pathway: current status and practical implications in molecular pharming.

International audiencePlants have become, over the last ten years, a suitable alternative to microbial and animal cell factories for the production of clinically-useful, therapeutic proteins. Besides the well known advantage of low-cost and large-scale production of safe and biologically active mammalian proteins, plants also are able to perform most post-translational maturations required for biological activity and suitable pharmacokinetics of recombinant therapeutic proteins. In this short review we focus on glycosylation and proteolytic processing of plant-made pharmaceuticals during their transport through the plant cell's secretory pathway. We also address the practical implications of these important processes on the effectiveness of plant molecular pharming systems

Isolated blast crisis relapse in the central nervous system of a patient treating for a chronic myelogenous leukemia

Chronic myeloid leukemia (CML) is a myeloproliferative disorder associated with the Philadelphia chromosome t (9;22) and the BCR-ABL fusion gene. The condition is relatively rare, accounting for 2.0% to 3.0% of childhood leukemia cases. CML has historically been a triphasic disease. Most patients are diagnosed in chronic phase. Without treatment, it inevitably progresses into a more aggressive accelerated phase and blast crisis. Some proportion of CML cases of blastic transformation develop an extramedullary disease that involves rarely central nervous system. This report describe an extremely rare case of 13-year-old girl with CML and extramedullary blast crisis in the central nervous system. Treatment options and monitoring of disease response are discussed

Stress-Responsive Mitogen-Activated Protein Kinases Interact with the EAR Motif of a Poplar Zinc Finger Protein and Mediate Its Degradation through the 26S Proteasome1[W][OA]

Mitogen-activated protein kinases (MAPKs) contribute to the establishment of plant disease resistance by regulating downstream signaling components, including transcription factors. In this study, we identified MAPK-interacting proteins, and among the newly discovered candidates was a Cys-2/His-2-type zinc finger protein named PtiZFP1. This putative transcription factor belongs to a family of transcriptional repressors that rely on an ERF-associated amphiphilic repression (EAR) motif for their repression activity. Amino acids located within this repression motif were also found to be essential for MAPK binding. Close examination of the primary protein sequence revealed a functional bipartite MAPK docking site that partially overlaps with the EAR motif. Transient expression assays in Arabidopsis (Arabidopsis thaliana) protoplasts suggest that MAPKs promote PtiZFP1 degradation through the 26S proteasome. Since features of the MAPK docking site are conserved among other EAR repressors, our study suggests a novel mode of defense mechanism regulation involving stress-responsive MAPKs and EAR repressors

Multimodal protein constructs for herbivore insect control

Transgenic plants expressing combinations of microbial or plant pesticidal proteins represent a promising tool for the efficient, durable control of herbivorous insects. In this review we describe current strategies devised for the heterologous co-expression of pesticidal proteins in planta, some of which have already shown usefulness in plant protection. Emphasis is placed on protein engineering strategies involving the insertion of single DNA constructs within the host plant genome. Multimodal fusion proteins integrating complementary pesticidal functions along a unique polypeptide are first considered, taking into account the structural constraints associated with protein or protein domain grafting to biologically active proteins. Strategies that allow for the co- or post-translational release of two or more pesticidal proteins are then considered, including polyprotein precursors releasing free proteins upon proteolytic cleavage, and multicistronic transcripts for the parallel translation of single protein-encoding mRNA sequences