The ubiquitin proteasome system in Caenorhabditis elegans and its regulation

Papaevgeniou, Nikoletta; Chondrogianni, Niki

doi:10.1016/j.redox.2014.01.007

Cited by 74 publications

(65 citation statements)

References 188 publications

(234 reference statements)

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“…The observed dependence is in agreement with studies in human (10,15,27) and yeast cells (7,32) and in multicellular organisms (8,46,55,58). It is, however, noteworthy that with the exception of quercetin (10) and 18a-GA (27) in all other mentioned studies, proteasome activation was achieved through genetic manipulation.…”

Section: Discussionsupporting

confidence: 89%

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression inCaenorhabditiselegansand Neuronal Cultures

Papaevgeniou

Sakellari

Jha

et al. 2016

Antioxidants & Redox Signaling

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Aims: Proteasomes are constituents of the cellular proteolytic networks that maintain protein homeostasis through regulated proteolysis of normal and abnormal (in any way) proteins. Genetically mediated proteasome activation in multicellular organisms has been shown to promote longevity and to exert protein antiaggregation activity. In this study, we investigate whether compound-mediated proteasome activation is feasible in a multicellular organism and we dissect the effects of such approach in aging and Alzheimer's disease (AD) progression. Results: Feeding of wild-type Caenorhabditis elegans with 18a-glycyrrhetinic acid (18a-GA; a previously shown proteasome activator in cell culture) results in enhanced levels of proteasome activities that lead to a skinhead-1-and proteasome activation-dependent life span extension. The elevated proteasome function confers lower paralysis rates in various AD nematode models accompanied by decreased Ab deposits, thus ultimately decelerating the progression of AD phenotype. More importantly, similar positive results are also delivered when human and murine cells of nervous origin are subjected to 18a-GA treatment. Innovation: This is the first report of the use of 18a-GA, a diet-derived compound as prolongevity and antiaggregation factor in the context of a multicellular organism. Conclusion: Our results suggest that proteasome activation with downstream positive outcomes on aging and AD, an aggregation-related disease, is feasible in a nongenetic manipulation manner in a multicellular organism. Moreover, they unveil the need for identification of antiaging and antiamyloidogenic compounds among the nutrients found in our normal diet. Antioxid. Redox Signal. 25, 855-869.

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Section: Discussionsupporting

confidence: 89%

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression inCaenorhabditiselegansand Neuronal Cultures

Papaevgeniou

Sakellari

Jha

et al. 2016

Antioxidants & Redox Signaling

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“…Newly synthesised but defective proteins, as well as functional proteins no longer needed, are modified to facilitate their entry into the proteasome complex for proteolysis by the cryptically positioned CT-L, PGPH and T-L enzymes (Tanaka et a l, 2012;Tanaka & Matsuda, 2014). Involve ment of the proteasome in the growth and oogenesis of Caenorhabditis elegans has been investigated (Pispa et al, 2008), and the C. elegans ubiquitin-proteasome sys tem is being explored in detail (Papaevgeniou & Chondrogianni, 2014) as a model for mammals. Parasitism by cyst nematodes is suspected of being aided by nematode secretions that affect the plant ubiquitin-proteasome sys tem (Davis et al, 2004;Chronis et al, 2013) but little is known about plant-parasitic nematode proteasomes.…”

Section: Discussionmentioning

confidence: 99%

“…The analogue epigallocatechin gallate (EGCG) affects a broad range of fundamental cellular metabolic processes, including proteolytic activities associated with the pro teasome (Bonfili et al, 2011;Singh et al, 2011). The proteasome is a large multi-subunit proteolytic complex, part of the ubiquitin proteasome system involved with maintaining cellular health through regulated proteoly sis (Glickman & Adir, 2004;Papaevgeniou & Chondrogianni, 2014). The 20S proteasome subunit contains E.P.…”

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confidence: 99%

“…M asler three proteases, chymotrypsin-like, trypsin-like and post glutamate peptide hydrolysing (caspase-like) enzymes. Together, these proteases account for ubiquinated-protein substrate degradation (Kisselev et a i, 2006;Papaevgeniou & Chondrogianni, 2014). The proteasome and its inhibition receive considerable attention in medical re search as a means to affect cellular metabolism and dis ease (Kisselev et al, 2012).…”

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confidence: 99%

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Protease inhibition by Heterodera glycines cyst content: evidence for effects on the Meloidogyne incognita proteasome

Masler¹

2015

Nematol

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Proteases from Heterodera glycines and Meloidogyne incognita juveniles were inhibited by heat-stable content from H. glycines cysts (hHglCE), and by a polyphenol (EGCG) similar to a compound previously identified in Globodera cysts. General protease activities detected using the nematode peptide KSAYMRFa were inhibited by EGCG (IC50 1.19 mM, H. glycines', 0.34 mM, M. incognita) but not by hHglCE. However, hHglCE and EGCG each inhibited proteasome-associated chymotrypsin-like (CT-L) activity. EGCG IC50 values were 0.47 mM (H. glycines) and 0.15 mM (M. incognita). hHglCE IC50 values were 0.16 and 0.005 mM hHglCEeq for H. glycines and M. incognita, respectively. Across all substrate-inhibitor combinations, M. incognita proteases were inhibited more robustly than those from H. glycines, particularly by hHglCE. In addition to CT-L protease, post-glutamate peptide hydrolysing (PGPH) and trypsin-like (T-L) proteasome proteases were detected in M. incognita, and each of these was also strongly inhibited by hHglCE. hHglCE inhibited CT-L, PGPH and T-L proteases within catalytic subunits from yeast (Saccharomyces cerevisiae) and human proteasomes. Proteasome inhibitors MG-132 and aclacinomycin A each inhibited M. incognita CT-L and PGPH activities by more than 80% at 20-100 gM , and hHglCE inhibited the same proteases by 70-80% at 0.04 hHglCEeq /zl_ l . hHglCE completely inhibited M. incognita T-L activity, but CT-L activity in native content from H. glycines cysts was not inhibited. Evidence that H. glycines cysts contain inhibitors of all proteases associated with the proteasome establishes the cyst as an important new target to explore for potential nematode control compounds. In addition, characterisation of protease activities from a core cellular metabolic component using M. incognita is novel for plant-parasitic nematodes.

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“…The 19S RP is divided into a lid and a base component. 10,21,22 The 19S base is composed of six ATPase subunits (RPT-1, RPT-2, RPT-3, RPT-4, RPT-5, and RPT-6) and four non-ATPases (RPN-1, RPN-2, RPN-10 and RPN-13). 22 The 19S lid particle is comprised of nine subunits: RPN-3, RPN-5, RPN-6.1, RPN-7, RPN-8, RPN-9, RPN-11, RPN-12 and RPN-15 (DSS-1).…”

Section: Introductionmentioning

confidence: 99%

TheC. elegansproteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality

Fernando

Elliot

Allén

2020

Preprint

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Background: The proteasome is a multi-subunit complex and a major proteolytic machinery in cells. Most subunits are essential for proteasome function, and depletion of individual subunits normally results in lethality. RPN-12/Rpn12/PSMD8 is a lid subunit of the 19S regulatory particle (RP) of the 26S proteasome. Studies in Caenorhabditis elegans demonstrated that RNAi depletion of RPN-12 does not result in lethality. RPN-12 has not been well studied in higher eukaryotes. In this study we investigate the biological significance of RPN-12 in C. elegans.Results: We found that the null mutant rpn-12(av93) did not cause major impairment of the proteolytic activity of the proteasome. Most rpn-12(av93) hermaphrodites lack sperm leading to feminization of the germ line that can be partially rescued by mating to males.The lack of sperm phenotype can be suppressed by downregulation of TRA-1, a player in the hermaphrodite germline sex determination pathway. Also, rpn-12(av93) animals show significant nuclear accumulation of the meiotic kinase WEE-1.3, a protein predominantly localized to the perinuclear region. Interestingly, chemical inhibition of the proteasome did not cause nuclear accumulation of WEE-1.3.Conclusions: RPN-12 plays a previously unknown role in oogenesis and the germline sex determination pathway in C. elegans hermaphrodites.

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The ubiquitin proteasome system in Caenorhabditis elegans and its regulation

Cited by 74 publications

References 188 publications

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression inCaenorhabditiselegansand Neuronal Cultures

18α-Glycyrrhetinic Acid Proteasome Activator Decelerates Aging and Alzheimer's Disease Progression inCaenorhabditiselegansand Neuronal Cultures

Protease inhibition by Heterodera glycines cyst content: evidence for effects on the Meloidogyne incognita proteasome

TheC. elegansproteasome subunit RPN-12 is required for hermaphrodite germline sex determination and oocyte quality

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