Ubiquitin-Proteasome System- a target to control pathogenic protozoa
نویسندگان
چکیده
Ubiquitin-proteasome system (UPS) is an ATP-dependent proteolytic machinery of eukaryotes. Analogous systems have been characterized in eubacteria and archaea as well. Although the structure and functions of this machinery is welldocumented in yeast and vertebrates, knowledge of this machinery is rudimentary for unicellular parasitic protozoa. This chapter summarizes the current knowledge regarding the UPS of Plasmodium, Entamoeba, Trypansoma, Leishmaina and Giardia, including the effect of proteasomal inhibition on these parasites. The unique variations of the UPS of each of these parasites have been highlighted as they may serve as potential therapeutic targets.
منابع مشابه
Exploitation of Eukaryotic Ubiquitin Signaling Pathways by Effectors Translocated by Bacterial Type III and Type IV Secretion Systems
The specific and covalent addition of ubiquitin to proteins, known as ubiquitination, is a eukaryotic-specific modification central to many cellular processes, such as cell cycle progression, transcriptional regulation, and hormone signaling. Polyubiquitination is a signal for the 26S proteasome to destroy earmarked proteins, but depending on the polyubiquitin chain topology, it can also result...
متن کاملUbiquitin proteasome dysfunction in human hypertrophic and dilated cardiomyopathies.
BACKGROUND The ubiquitin proteasome system maintains a dynamic equilibrium of proteins and prevents accumulation of damaged and misfolded proteins, yet its role in human cardiac dysfunction is not well understood. The present study evaluated ubiquitin proteasome system function in human heart failure and hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS Proteasome function was studied in...
متن کاملThe Ubiquitin-Proteasome System and F-box Proteins in Pathogenic Fungi
The ubiquitin-proteasome system is one of the major protein turnover mechanisms that plays important roles in the regulation of a variety of cellular functions. It is composed of E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3 ubiquitin ligases that transfer ubiquitin to the substrates that are subjected to degradation in the 26S proteasome. The Skp1, Cullin, F-box p...
متن کاملCharacterization of the 26S proteasome network in Plasmodium falciparum
In eukaryotic cells, the ubiquitin-proteasome system as a key regulator of protein quality control is an excellent drug target. We therefore aimed to analyze the 26S proteasome complex in the malaria parasite Plasmodium falciparum, which still threatens almost half of the world's population. First, we established an affinity purification protocol allowing for the isolation of functional 26S pro...
متن کاملRole of the Ubiquitin-Proteasome Systems in the Biology and Virulence of Protozoan Parasites
In eukaryotic cells, proteasomes perform crucial roles in many cellular pathways by degrading proteins to enforce quality control and regulate many cellular processes such as cell cycle progression, signal transduction, cell death, immune responses, metabolism, protein-quality control, and development. The catalytic heart of these complexes, the 20S proteasome, is highly conserved in bacteria, ...
متن کامل