scholarly journals Vms1p is a release factor for the Ribosome-associated Quality control Complex

2018 ◽  
Author(s):  
Olga Zurita Rendón ◽  
Eric K. Fredrickson ◽  
Conor J. Howard ◽  
Jonathan Van Vranken ◽  
Sarah Fogarty ◽  
...  
Keyword(s):  
Quality Control ◽  
Ubiquitin Proteasome System ◽  
The Novel ◽  
Novel Proteins ◽  
Lysine Residues ◽  
Nascent Chain ◽  
Ubiquitin Proteasome ◽  
Exit Tunnel ◽  
Carboxy Terminal ◽  
Control Complex

Eukaryotic cells employ the Ribosome-associated Quality control Complex (RQC) to maintain homeostasis despite defects that cause ribosomes to stall. The RQC comprises the E3 ubiquitin ligase Ltn1p, the ATPase Cdc48p, and the novel proteins Rqc1p and Rqc2p1–3. Following recognition and subunit splitting of stalled ribosomes, the RQC detects and assembles on 60S subunits that hold incomplete polypeptides linked to a tRNA (60S:peptidyl–tRNA)4–8. Ltn1p cooperates with Rqc1p to facilitate ubiquitination of the incomplete nascent chain, marking it for degradation7,9,10. Rqc2p stabilizes Ltn1p on the 60S3–5,8 and recruits charged tRNAs to the 60S to catalyze elongation of the nascent protein with Carboxy-terminal Alanine and Threonine extensions, or CAT tails, via a mechanism that is distinct from canonical translation4,10. CAT-tailing mobilizes and exposes lysine residues in the nascent chain, especially those stalled within the exit tunnel, thereby supporting efficient ubiquitination10,11. If the ubiquitin-proteasome system is overwhelmed or unavailable, CAT-tailed nascent chains aggregate in the cytosol or within organelles like the mitochondria12–14. Here we identify Vms1p as the tRNA hydrolase that releases nascent polypeptides for extraction and degradation in the RQC pathway.

scholarly journals TTC3-Mediated Protein Quality Control, A Potential Mechanism for Cognitive Impairment

2021 ◽  
Author(s):  
Xu Zhou ◽  
Xiongjin Chen ◽  
Tingting Hong ◽  
Miaoping Zhang ◽  
Yujie Cai ◽  
...  
Keyword(s):  
Quality Control ◽  
Cognitive Impairment ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Research Progress ◽  
Repeat Domain ◽  
Ubiquitin Proteasome ◽  
Domain 3

AbstractThe tetrapeptide repeat domain 3 (TTC3) gene falls within Down's syndrome (DS) critical region. Cognitive impairment is a common phenotype of DS and Alzheimer’s disease (AD), and overexpression of TTC3 can accelerate cognitive decline, but the specific mechanism is unknown. The TTC3-mediated protein quality control (PQC) mechanism, similar to the PQC system, is divided into three parts: it acts as a cochaperone to assist proteins in folding correctly; it acts as an E3 ubiquitin ligase (E3s) involved in protein degradation processes through the ubiquitin–proteasome system (UPS); and it may also eventually cause autophagy by affecting mitochondrial function. Thus, this article reviews the research progress on the structure, function, and metabolism of TTC3, including the recent research progress on TTC3 in DS and AD; the role of TTC3 in cognitive impairment through PQC in combination with the abovementioned attributes of TTC3; and the potential targets of TTC3 in the treatment of such diseases.

scholarly journals A Yeast-Based Functional Assay to Study Plant N-Degron – N-Recognin Interactions

2022 ◽  
Vol 12 ◽  
Author(s):  
Aida Kozlic ◽  
Nikola Winter ◽  
Theresia Telser ◽  
Jakob Reimann ◽  
Katrin Rose ◽  
...  
Keyword(s):  
Ubiquitin Proteasome System ◽  
Functional Assay ◽  
The Novel ◽  
In Planta ◽  
Amino Terminal ◽  
Weak Binding ◽  
Ubiquitin Conjugating Enzyme ◽  
Ubiquitin Proteasome ◽  
The Stability

The N-degron pathway is a branch of the ubiquitin-proteasome system where amino-terminal residues serve as degradation signals. In a synthetic biology approach, we expressed ubiquitin ligase PRT6 and ubiquitin conjugating enzyme 2 (AtUBC2) from Arabidopsis thaliana in a Saccharomyces cerevisiae strain with mutation in its endogenous N-degron pathway. The two enzymes re-constitute part of the plant N-degron pathway and were probed by monitoring the stability of co-expressed GFP-linked plant proteins starting with Arginine N-degrons. The novel assay allows for straightforward analysis, whereas in vitro interaction assays often do not allow detection of the weak binding of N-degron recognizing ubiquitin ligases to their substrates, and in planta testing is usually complex and time-consuming.

scholarly journals Rqc2p and 60S ribosomal subunits mediate mRNA-independent elongation of nascent chains

Science ◽  
2015 ◽  
Vol 347 (6217) ◽  
pp. 75-78 ◽  
Author(s):  
Peter S. Shen ◽  
Joseph Park ◽  
Yidan Qin ◽  
Xueming Li ◽  
Krishna Parsawar ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Transfer Rna ◽  
Exit Channel ◽  
Ribosomal Subunits ◽  
Cryo Electron Microscopy ◽  
Nascent Chain ◽  
New Gene ◽  
Carboxy Terminal ◽  
A Site ◽  
Control Complex

In Eukarya, stalled translation induces 40S dissociation and recruitment of the ribosome quality control complex (RQC) to the 60S subunit, which mediates nascent chain degradation. Here we report cryo–electron microscopy structures revealing that the RQC components Rqc2p (YPL009C/Tae2) and Ltn1p (YMR247C/Rkr1) bind to the 60S subunit at sites exposed after 40S dissociation, placing the Ltn1p RING (Really Interesting New Gene) domain near the exit channel and Rqc2p over the P-site transfer RNA (tRNA). We further demonstrate that Rqc2p recruits alanine- and threonine-charged tRNA to the A site and directs the elongation of nascent chains independently of mRNA or 40S subunits. Our work uncovers an unexpected mechanism of protein synthesis, in which a protein—not an mRNA—determines tRNA recruitment and the tagging of nascent chains with carboxy-terminal Ala and Thr extensions (“CAT tails”).

Amyloid Beta

2019 ◽  
pp. 235-251
Author(s):  
Abhinav Anand ◽  
Neha Sharma ◽  
Monica Gulati ◽  
Navneet Khurana
Keyword(s):  
Amyloid Beta ◽  
Cognitive Abilities ◽  
Neurodegenerative Disorder ◽  
Proteolytic Enzymes ◽  
Ubiquitin Proteasome System ◽  
The Novel ◽  
Ubiquitin Proteasome ◽  
Causes Of Deaths ◽  
Brain Acetylcholine ◽  
The Brain

Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.

Amyloid Beta

2021 ◽  
pp. 1-17
Author(s):  
Abhinav Anand ◽  
Neha Sharma ◽  
Monica Gulati ◽  
Navneet Khurana
Keyword(s):  
Amyloid Beta ◽  
Cognitive Abilities ◽  
Neurodegenerative Disorder ◽  
Proteolytic Enzymes ◽  
Ubiquitin Proteasome System ◽  
The Novel ◽  
Ubiquitin Proteasome ◽  
Causes Of Deaths ◽  
Brain Acetylcholine ◽  
The Brain

Alzheimer's disease (AD), exhibiting accumulation of amyloid beta (Aβ) peptide as a foremost protagonist, is one of the top five causes of deaths. It is a neurodegenerative disorder (ND) that causes a progressive decline in memory and cognitive abilities. It is characterized by deposition of Aβ plaques and neurofibrillary tangles (NFTs) in the neurons, which in turn causes a decline in the brain acetylcholine levels. Aβ hypothesis is the most accepted hypothesis pertaining to the pathogenesis of AD. Amyloid Precursor Protein (APP) is constitutively present in brain and it is cleaved by three proteolytic enzymes (i.e., alpha, beta, and gamma secretases). Beta and gamma secretases cleave APP to form Aβ. Ubiquitin Proteasome System (UPS) is involved in the clearing of Aβ plaques. AD also involves impairment in UPS. The novel disease-modifying approaches involve inhibition of beta and gamma secretases. A number of clinical trials are going on worldwide with moieties targeting beta and gamma secretases. This chapter deals with an overview of APP and its enzymatic cleavage leading to AD.

Protein Quality Control in Neurodegeneration and Neuroprotection

2020 ◽  
pp. 1-24
Author(s):  
Yasmeena Akhter ◽  
Jahangir Nabi ◽  
Hinna Hamid ◽  
Nahida Tabassum ◽  
Faheem Hyder Pottoo ◽  
...  
Keyword(s):  
Quality Control ◽  
Neurodegenerative Disorders ◽  
Protein Quality ◽  
Protein Quality Control ◽  
Ubiquitin Proteasome System ◽  
Security System ◽  
Conformational Disorders ◽  
Ubiquitin Proteasome ◽  
Multi Level

Proteostasis is essential for regulating the integrity of the proteome. Disruption of proteostasis under some rigorous conditions leads to the aggregation and accumulation of misfolded toxic proteins, which plays a central role in the pathogenesis of protein conformational disorders. The protein quality control (PQC) system serves as a multi-level security system to shield cells from abnormal proteins. The intrinsic PQC systems maintaining proteostasis include the ubiquitin-proteasome system (UPS), chaperon-mediated autophagy (CMA), and autophagy-lysosome pathway (ALP) that serve to target misfolded proteins for unfolding, refolding, or degradation. Alterations of PQC systems in neurons have been implicated in the pathogenesis of various neurodegenerative disorders. This chapter provides an overview of PQC pathways to set a framework for discussion of the role of PQC in neurodegenerative disorders. Additionally, various pharmacological approaches targeting PQC are summarized.

Quality Control of Gastric Proton Pump in the Endoplasmic Reticulum by Ubiquitin/Proteasome System

2003 ◽  
Vol 986 (1) ◽  
pp. 655-657
Author(s):  
SHINJI ASANO ◽  
TOHRU KIMURA ◽  
HOKARA ISHIZUKA ◽  
MAGOTOSHI MORII ◽  
NORIAKI TAKEGUCHI
Keyword(s):  
Quality Control ◽  
Endoplasmic Reticulum ◽  
Proton Pump ◽  
Ubiquitin Proteasome System ◽  
Ubiquitin Proteasome ◽  
Gastric Proton Pump
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