Plants utilize different molecular mechanisms, including the Ubiquitin Proteasome System (UPS) that facilitates changes to the proteome, to mitigate the impact of abiotic stresses on growth and development. The UPS encompasses the ubiquitination of selected substrates followed by the proteasomal degradation of the modified proteins. Ubiquitin ligases, or E3s, are central to the UPS as they govern specificity and facilitate the attachment of one or more ubiquitin molecules to the substrate protein. From recent studies, the UPS has emerged as an important regulator of the uptake and translocation of essential macronutrients and micronutrients. In this review, we discuss select E3s that are involved in regulating nutrient uptake and responses to stress conditions, including limited or excess levels of nitrogen, phosphorus, iron, and copper.
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http://dx.doi.org/10.3389/fpls.2022.867419 | DOI Listing |
Proteolysis targeting chimeras (PROTACs) are pivotal in cancer therapy for their ability to degrade specific proteins. However, their non-specificity can lead to systemic toxicity due to protein degradation in normal cells. To address this, we have integrated a nanobody into the PROTACs framework and leveraged the tumor microenvironment to enhance drug specificity.
View Article and Find Full Text PDFTo 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 PDFIndoleamine 2,3-dioxygenase 1 (IDO1) is a potently immunosuppressive protein that inhibits antitumor immunity through both tryptophan metabolism and non-enzymatic functions. Pharmacological therapies targeting IDO1 enzyme activity have generally failed to improve the overall survival of patients with cancer. Developing new therapeutic agents that are capable of neutralizing both enzyme-and non-enzyme-derived immunosuppressive IDO1 effects is therefore of high interest.
View Article and Find Full Text PDFBiol Chem
January 2025
Cell Biology, 26562 RPTU University of Kaiserslautern, Erwin-Schrödinger-Strasse 13, D-67663 Kaiserslautern, Germany.
Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If the rate of protein synthesis exceeds the capacity of the mitochondrial import machinery, precursor proteins can transiently accumulate in the cytosol. The cytosolic accumulation of mitochondrial precursors jeopardizes cellular protein homeostasis (proteostasis) and can be the cause of diseases.
View Article and Find Full Text PDFSci Rep
January 2025
Jiangsu Key Laboratory of Marine Pharmaceutical Compound Screening, College of Pharmacy, Jiangsu Ocean University, Lianyungang, 222005, China.
The ubiquitin-proteasome system (UPS) is essential for cellular homeostasis, regulating the degradation of proteins involved in key processes such as cell cycle, apoptosis, and DNA repair. Dysregulation of the UPS is implicated in hepatocellular carcinoma (HCC), contributing to tumor progression and therapeutic resistance. The cereblon (CRBN) E3 ubiquitin ligase complex is a crucial component of the UPS, particularly in modulating protein degradation in response to small-molecule modulators like thalidomide.
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