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26S proteasome

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https://www.readbyqxmd.com/read/28447215/interplay-between-recombinant-hsp70-and-proteasomes-proteasome-activity-modulation-and-ubiquitin-independent-cleavage-of-hsp70
#1
Alexey V Morozov, Tatiana M Astakhova, David G Garbuz, George S Krasnov, Natalia V Bobkova, Olga G Zatsepina, Vadim L Karpov, Michail B Evgen'ev
The heat shock protein 70 (Hsp70, human HSPA1A) plays indispensable roles in cellular stress responses and protein quality control (PQC). In the framework of PQC, it cooperates with the ubiquitin-proteasome system (UPS) to clear damaged and dysfunctional proteins in the cell. Moreover, Hsp70 itself is rapidly degraded following the recovery from stress. It was demonstrated that its fast turnover is mediated via ubiquitination and subsequent degradation by the 26S proteasome. At the same time, the effect of Hsp70 on the functional state of proteasomes has been insufficiently investigated...
April 26, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28443108/the-kinase-activity-of-calcineurin-b-like-interacting-protein-kinase-26-cipk26-influences-its-own-stability-and-that-of-the-aba-regulated-ubiquitin-ligase-keep-on-going-keg
#2
Wendy J Lyzenga, Victoria Sullivan, Hongxia Liu, Sophia L Stone
The Really Interesting New Gene (RING)-type E3 ligase, Keep on Going (KEG) plays a critical role in Arabidopsis growth after germination and the connections between KEG and hormone signaling pathways are expanding. With regards to abscisic acid (ABA) signaling, KEG targets ABA-responsive transcription factors abscisic acid insensitive 5, ABF1 and ABF3 for ubiquitination and subsequent degradation through the 26S proteasome. Regulation of E3 ligases through self-ubiquitination is common to RING-type E3 ligases and ABA promotes KEG self-ubiquitination and degradation...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28442575/structure-and-energetics-of-pairwise-interactions-between-proteasome-subunits-rpn2-rpn13-and-ubiquitin-clarify-a-substrate-recruitment-mechanism
#3
Ryan T VanderLinden, Casey W Hemmis, Tingting Yao, Howard Robinson, Christopher P Hill
The 26S proteasome is a large cellular assembly that mediates the selective degradation of proteins in the nucleus and cytosol and is an established target for anti-cancer therapeutics. Protein substrates are typically targeted to the proteasome through modification with a polyubiquitin chain, which can be recognized by several proteasome-associated ubiquitin receptors. One of these receptors, RPN13/ADRM1, is recruited to the proteasome through direct interaction with the large scaffolding protein RPN2 within the 19S regulatory particle...
April 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28441582/synthesis-and-antiproteasomal-activity-of-novel-o-benzyl-salicylamide-based-inhibitors-built-from-leucine-and-phenylalanine
#4
Radek Jorda, Jan Dušek, Eva Řezníčková, Karel Pauk, Pratibha P Magar, Aleš Imramovský, Vladimír Kryštof
Inhibition of protein degradation is one of strategies for suppression of uncontrolled proliferation of cancer cells. Proteolytic degradation in cells is mainly ensured by proteasome and its inhibition by bortezomib showed benefit in clinical use for the treatment of multiple myeloma. We report here the library of antiproteasomal O-benzyl salicylamides built from leucine and phenylalanine. Prepared compounds displayed antiproliferative activity on K562, CEM and U266 cancer cell lines, ranging from high micromolar to submicromolar GI50 values...
April 15, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28420710/reciprocal-proteasome-mediated-degradation-of-pifs-and-hfr1-underlying-photomorphogenic-development-in-arabidopsis
#5
Xiaosa Xu, Praveen Kumar Kathare, Vinh Ngoc Pham, Qingyun Bu, Andrew Nguyen, Enamul Huq
The phytochrome-mediated regulation of photomorphogenesis under red and far-red light conditions involves both positive and negatively acting factors. The positively acting factors (e.g., HY5/HFR1/LAF1 and others) are degraded in the dark to prevent photomorphogenesis. By contrast, the negatively acting factors (e.g., PIFs) are degraded in response to light to promote photomorphogenesis. Here we show that the negatively acting factor, PIF1 is also degraded in the dark by direct heterodimerization with the positively acting factor, HFR1...
April 18, 2017: Development
https://www.readbyqxmd.com/read/28416611/the-deubiquitinating-enzyme-usp14-allosterically-inhibits-multiple-proteasomal-activities-and-ubiquitin-independent-proteolysis
#6
Hyoung Tae Kim, Alfred L Goldberg
The proteasome-associated deubiquitinating enzyme Usp14/Ubp6 inhibits protein degradation by catalyzing substrate deubiquitination and by poorly understood allosteric actions. However, upon binding a ubiquitin chain, Usp14 enhances proteasomal degradation by stimulating ATP and peptide degradation. These studies were undertaken to clarify these seemingly opposite regulatory roles of Usp14 and their importance. To learn how the presence of Usp14 on 26S proteasomes influences its different activities, we compared enzymatic and regulatory properties of 26S proteasomes purified from wild type MEF cells and ones lacking Usp14...
April 17, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28404519/proteasome-inhibitors-to-alleviate-aberrant-ikbkap-mrna-splicing-and-low-ikap-help1-synthesis-in-familial-dysautonomia
#7
Mylène Hervé, El Chérif Ibrahim
FD is a rare neurodegenerative disorder caused by a mutation of the IKBKAP gene, which induces low expression levels of the Elongator subunit IKAP/hELP1 protein. A rational strategy for FD treatment could be to identify drugs increasing IKAP/hELP1 expression levels by blocking protein degradation pathways such as the 26S proteasome. Proteasome inhibitors are promising molecules emerging in cancer treatment and could thus constitute an enticing pharmaceutical strategy for FD treatment. Therefore, we tested three proteasome inhibitors on FD human olfactory ecto-mesenchymal stem cells (hOE-MSCs): two approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA), bortezomib and carfilzomib, as well as epoxomicin...
April 9, 2017: Neurobiology of Disease
https://www.readbyqxmd.com/read/28403546/downregulation-of-delta-aminolevulinate-dehydratase-is-associated-with-poor-prognosis-in%C3%A2-patients-with-breast-cancer
#8
Jie Ge, Yue Yu, Fei Xin, Zheng-Jun Yang, Hong-Meng Zhao, Xin Wang, Zhong-Sheng Tong, Xu-Chen Cao
Delta-aminolevulinate dehydratase (ALAD) catalyzes the second step in the biosynthesis of heme and is also an endogenous inhibitor of the 26S proteasome. The role of ALAD in breast cancer progression is still unclear. In this study, we found that the expression of ALAD was downregulated in breast cancer tissues compared with adjacent normal breast tissues. Enhanced ALAD expression was associated with a favorable outcome in patients with breast cancer. Overexpression of ALAD suppresses breast cancer cell proliferation and invasion and inhibits the epithelial-mesenchymal transition phenotype...
February 3, 2017: Cancer Science
https://www.readbyqxmd.com/read/28396515/light-involved-regulation-of-bzr1-stability-andphosphorylation-statusto-coordinate-plant-growth-in-arabidopsis
#9
Qian-Feng Li, Li-Chun Huang, Ke Wei, Jia-Wen Yu, Chang-Quan Zhang, Qiao-Quan Liu
Light and Brassinosteroid (BR) are master environmental stimulus and endogenous cue for plant growth and development, respectively. Great progress has been made in elucidating the molecular mechanisms on the crosstalk between light and BR. However, little is known about how BZR1, the pivotal integration node, is regulated by light and dark. Here, we demonstrated that an intact BR signaling pathway is essential for dark-induced hypocotyl elongation. Consequent expression assay showed that light-dark switch affected BZR1 phosphorylation and accumulation...
April 10, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28396430/in-situ-structural-studies-of-tripeptidyl-peptidase-ii-tppii-reveal-spatial-association-with-proteasomes
#10
Yoshiyuki Fukuda, Florian Beck, Jürgen M Plitzko, Wolfgang Baumeister
Tripeptidyl peptidase II (TPPII) is a eukaryotic protease acting downstream of the 26S proteasome; it removes tripeptides from the degradation products released by the proteasome. Structural studies in vitro have revealed the basic architecture of TPPII, a two-stranded linear polymer that assembles to form a spindle-shaped complex of ∼6 MDa. Dependent on protein concentration, TPPII has a distinct tendency for polymorphism. Therefore, its structure in vivo has remained unclear. To resolve this issue, we have scrutinized cryo-electron tomograms of rat hippocampal neurons for the occurrence and spatial distribution of TPPII by template matching...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28396413/ubiquitinated-proteins-promote-the-association-of-proteasomes-with-the-deubiquitinating-enzyme-usp14-and-the-ubiquitin-ligase-ube3c
#11
Chueh-Ling Kuo, Alfred Lewis Goldberg
In mammalian cells, the 26S proteasomes vary in composition. In addition to the standard 28 subunits in the 20S core particle and 19 subunits in each 19S regulatory particle, a small fraction (about 10-20% in our preparations) also contains the deubiquitinating enzyme Usp14/Ubp6, which regulates proteasome activity, and the ubiquitin ligase, Ube3c/Hul5, which enhances proteasomal processivity. When degradation of ubiquitinated proteins in cells was inhibited, levels of Usp14 and Ube3c on proteasomes increased within minutes...
April 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28381880/20s-immunoproteasomes-remove-formaldehyde-damaged-cytoplasmic-proteins-suppressing-caspase-independent-cell-death
#12
Sara Ortega-Atienza, Casey Krawic, Lauren Watts, Caitlin McCarthy, Michal W Luczak, Anatoly Zhitkovich
Immunoproteasomes are known for their involvement in antigen presentation. However, their broad tissue presence and other evidence are indicative of nonimmune functions. We examined a role for immunoproteasomes in cellular responses to the endogenous and environmental carcinogen formaldehyde (FA) that binds to cytosolic and nuclear proteins producing proteotoxic stress and genotoxic DNA-histone crosslinks. We found that immunoproteasomes were important for suppression of a caspase-independent cell death and the long-term survival of FA-treated cells...
April 5, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28372990/neurotoxic-mechanisms-by-which-the-usp14-inhibitor-iu1-depletes-ubiquitinated-proteins-and-tau-in-rat-cerebral-cortical-neurons-relevance-to-alzheimer-s-disease
#13
Magdalena J Kiprowska, Anna Stepanova, Dustin R Todaro, Alexander Galkin, Arthur Haas, Scott M Wilson, Maria E Figueiredo-Pereira
In Alzheimer's disease proteasome activity is reportedly downregulated, thus increasing it could be therapeutically beneficial. The proteasome-associated deubiquitinase USP14 disassembles polyubiquitin-chains, potentially delaying proteasome-dependent protein degradation. We assessed the protective efficacy of inhibiting or downregulating USP14 in rat and mouse (Usp14(axJ)) neuronal cultures treated with prostaglandin J2 (PGJ2). IU1 concentrations (HIU1>25μM) reported by others to inhibit USP14 and be protective in non-neuronal cells, reduced PGJ2-induced Ub-protein accumulation in neurons...
March 31, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28360921/the-involvement-of-heat-shock-proteins-in-the-establishment-of-tomato-yellow-leaf-curl-virus-infection
#14
REVIEW
Rena Gorovits, Henryk Czosnek
Tomato yellow leaf curl virus (TYLCV), a begomovirus, induces protein aggregation in infected tomatoes and in its whitefly vector Bemisia tabaci. The interactions between TYLCV and HSP70 and HSP90 in plants and vectors are necessity for virus infection to proceed. In infected host cells, HSP70 and HSP90 are redistributed from a soluble to an aggregated state. These aggregates contain, together with viral DNA/proteins and virions, HSPs and components of the protein quality control system such as ubiquitin, 26S proteasome subunits, and the autophagy protein ATG8...
2017: Frontiers in Plant Science
https://www.readbyqxmd.com/read/28358323/identification-of-a-ribose-phosphate-pyrophosphokinase-that-can-interact-in-vivo-with-the-anaphase-promoting-complex-cyclosome
#15
Haiyang Yu, Yu Zhang, Dong Zhang, Yanxi Lu, Haixia He, Fucong Zheng, Meng Wang
5-Phospho-d-ribosyl-1-diphosphate (PRPP) synthase (PRS) catalyzes the biosynthesis of PRPP, which is an important compound of metabolism in most organisms. However, no PRS genes have been cloned, let alone studied for their biological function in rubber tree. In this study, we identify a novel protein (PRS4) that interacts in vivo with rubber tree anaphase promoting complex/cyclosome (APC/C) subunit 10 (HbAPC10) by yeast two-hybrid assays. PRS4 has been cloned from rubber tree and named as HbPRS4. Blastp search in the genome of Arabidopsis thaliana showed that HbPRS4 shared the highest similarity with AtPRS4, with 80...
March 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28343629/biallelic-variants-in-otud6b-cause-an-intellectual-disability-syndrome-associated-with-seizures-and-dysmorphic-features
#16
Teresa Santiago-Sim, Lindsay C Burrage, Frédéric Ebstein, Mari J Tokita, Marcus Miller, Weimin Bi, Alicia A Braxton, Jill A Rosenfeld, Maher Shahrour, Andrea Lehmann, Benjamin Cogné, Sébastien Küry, Thomas Besnard, Bertrand Isidor, Stéphane Bézieau, Isabelle Hazart, Honey Nagakura, LaDonna L Immken, Rebecca O Littlejohn, Elizabeth Roeder, Bulent Kara, Katia Hardies, Sarah Weckhuysen, Patrick May, Johannes R Lemke, Orly Elpeleg, Bassam Abu-Libdeh, Kiely N James, Jennifer L Silhavy, Mahmoud Y Issa, Maha S Zaki, Joseph G Gleeson, John R Seavitt, Mary E Dickinson, M Cecilia Ljungberg, Sara Wells, Sara J Johnson, Lydia Teboul, Christine M Eng, Yaping Yang, Peter-Michael Kloetzel, Jason D Heaney, Magdalena A Walkiewicz
Ubiquitination is a posttranslational modification that regulates many cellular processes including protein degradation, intracellular trafficking, cell signaling, and protein-protein interactions. Deubiquitinating enzymes (DUBs), which reverse the process of ubiquitination, are important regulators of the ubiquitin system. OTUD6B encodes a member of the ovarian tumor domain (OTU)-containing subfamily of deubiquitinating enzymes. Herein, we report biallelic pathogenic variants in OTUD6B in 12 individuals from 6 independent families with an intellectual disability syndrome associated with seizures and dysmorphic features...
April 6, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/28334815/gcn5-mediated-rph1-acetylation-regulates-its-autophagic-degradation-under-dna-damage-stress
#17
Feng Li, Liang-De Zheng, Xin Chen, Xiaolu Zhao, Scott D Briggs, Hai-Ning Du
Histone modifiers regulate proper cellular activities in response to various environmental stress by modulating gene expression. In budding yeast, Rph1 transcriptionally represses many DNA damage or autophagy-related gene expression. However, little is known how Rph1 is regulated during these stress conditions. Here, we report that Rph1 is degraded upon DNA damage stress conditions. Notably, this degradation occurs via the autophagy pathway rather than through 26S proteasome proteolysis. Deletion of ATG genes or inhibition of vacuole protease activity compromises Rph1 turnover...
February 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28330605/polyubiquitin-photoactivatable-crosslinking-reagents-for-mapping-ubiquitin-interactome-identify-rpn1-as-a-proteasome-ubiquitin-associating-subunit
#18
Michal Chojnacki, Wissam Mansour, Dharjath S Hameed, Rajesh K Singh, Farid El Oualid, Rina Rosenzweig, Mark A Nakasone, Zanlin Yu, Fabian Glaser, Lewis E Kay, David Fushman, Huib Ovaa, Michael H Glickman
Ubiquitin (Ub) signaling is a diverse group of processes controlled by covalent attachment of small protein Ub and polyUb chains to a range of cellular protein targets. The best documented Ub signaling pathway is the one that delivers polyUb proteins to the 26S proteasome for degradation. However, studies of molecular interactions involved in this process have been hampered by the transient and hydrophobic nature of these interactions and the lack of tools to study them. Here, we develop Ub-phototrap (Ub(PT)), a synthetic Ub variant containing a photoactivatable crosslinking side chain...
April 20, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28324352/the-six-tomato-yellow-leaf-curl-virus-genes-expressed-individually-in-tomato-induce-different-levels-of-plant-stress-response-attenuation
#19
Rena Gorovits, Adi Moshe, Linoy Amrani, Rotem Kleinberger, Ghandi Anfoka, Henryk Czosnek
Tomato yellow leaf curl virus (TYLCV) is a begomovirus infecting tomato plants worldwide. TYLCV needs a healthy host environment to ensure a successful infection cycle for long periods. Hence, TYLCV restrains its destructive effect and induces neither a hypersensitive response nor cell death in infected tomatoes. On the contrary, TYLCV counteracts cell death induced by other factors, such as inactivation of HSP90 functionality. Suppression of plant death is associated with the inhibition of the ubiquitin 26S proteasome degradation and with a deactivation of the heat shock transcription factor HSFA2 pathways (including decreased HSP17 levels)...
March 21, 2017: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/28322792/molecular-chaperones-of-the-hsp70-family-assist-in-the-assembly-of-20s-proteasomes
#20
Lindsay J Hammack, Kyle Firestone, William Chang, Andrew R Kusmierczyk
The eukaryotic 26S proteasome is a large protease comprised of two major sub assemblies, the 20S proteasome, or core particle (CP), and the 19S regulatory particle (RP). Assembly of the CP and RP is assisted by an expanding list of dedicated assembly factors. For the CP, this includes Ump1 and the heterodimeric Pba1-Pba2 and Pba3-Pba4 proteins. It is not known how many additional proteins that assist in proteasome biogenesis remain to be discovered. Here, we demonstrate that two members of the Hsp70 family in yeast, Ssa1 and Ssa2, play a direct role in CP assembly...
March 18, 2017: Biochemical and Biophysical Research Communications
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