Characterization of the 26S proteasome network in Plasmodium falciparum.

Sci Rep

Biochemistry and Molecular Biology, Interdisciplinary Research Center, Justus Liebig University, Giessen, Germany.

Published: December 2015

AI Article Synopsis

Article Abstract

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 proteasome complexes from the parasite. Subunit composition of the proteasome and component stoichiometry were studied and physiologic interacting partners were identified via in situ protein crosslinking. Furthermore, intrinsic ubiquitin receptors of the plasmodial proteasome were determined and their roles in proteasomal substrate recognition were analyzed. Notably, PfUSP14 was characterized as a proteasome-associated deubiquitinase resulting in the concept that targeting proteasomal deubiquitinating activity in P. falciparum may represent a promising antimalarial strategy. The data provide insights into a profound network orchestrated by the plasmodial proteasome and identified novel drug target candidates in the ubiquitin-proteasome system.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671066PMC
http://dx.doi.org/10.1038/srep17818DOI Listing

Publication Analysis

Top Keywords

26s proteasome
12
plasmodium falciparum
8
ubiquitin-proteasome system
8
drug target
8
plasmodial proteasome
8
proteasome
6
characterization 26s
4
proteasome network
4
network plasmodium
4
falciparum eukaryotic
4

Similar Publications

As a crucial post-translational modification (PTM), protein ubiquitination mediates the breakdown of particular proteins, which plays a pivotal role in a large number of biological processes including plant growth, development, and stress response. The ubiquitin-proteasome system (UPS) consists of ubiquitin (Ub), ubiquitinase, deubiquitinating enzyme (DUB), and 26S proteasome mediates more than 80% of protein degradation for protein turnover in plants. For the ubiquitinases, including ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2), and ubiquitin ligase (E3), the FBK (F-box Kelch repeat protein) is an essential component of multi-subunit E3 ligase SCF (Skp1-Cullin 1-F-box) involved in the specific recognition of target proteins in the UPS.

View Article and Find Full Text PDF

Tetrandrine (TET), a natural bisbenzyl isoquinoline alkaloid extracted from S. Moore, has diverse pharmacological effects. However, its effects on melanoma remain unclear.

View Article and Find Full Text PDF

26S Proteasome Subunit SlPBB2 Regulates Fruit Development and Ripening in Tomato.

J Agric Food Chem

January 2025

Fruit Biology Laboratory, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.

Proteasomes are protein complexes responsible for degrading unneeded or damaged proteins through proteolysis and play critical roles in regulating plant development and response to environmental stresses. However, it is still unclear whether proteasomes regulate fruit development and ripening. In this study, we investigated the function of a core proteasome subunit, SlPBB2, in tomato fruit.

View Article and Find Full Text PDF

Intracellular proteins take part in almost every body function; thus, protein homeostasis is of utmost importance. The ubiquitin proteasome system (UPS) has a fundamental role in protein homeostasis. Its main role is to selectively eradicate impaired or misfolded proteins, thus halting any damage that could arise from the accumulation of these malfunctioning proteins.

View Article and Find Full Text PDF

To direct regulated protein degradation, the 26S proteasome recognizes ubiquitinated substrates through its 19S particle and then degrades them in the 20S enzymatic core. Despite this close interdependency between proteasome subunits, we demonstrate that knockouts from different proteasome subcomplexes result in distinct highly cellular phenotypes. In particular, depletion of 19S PSMD lid proteins, but not that of other proteasome subunits, prevents bipolar spindle assembly during mitosis, resulting in a mitotic arrest.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!