A PHP Error was encountered

Severity: Warning

Message: fopen(/var/lib/php/sessions/ci_session6i8log66lqj5luds0uigcai7ih8qmelo): Failed to open stream: No space left on device

Filename: drivers/Session_files_driver.php

Line Number: 177

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

A PHP Error was encountered

Severity: Warning

Message: session_start(): Failed to read session data: user (path: /var/lib/php/sessions)

Filename: Session/Session.php

Line Number: 137

Backtrace:

File: /var/www/html/index.php
Line: 316
Function: require_once

N-degron pathways. | LitMetric

N-degron pathways.

Proc Natl Acad Sci U S A

Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, CA 91125.

Published: September 2024

An N-degron is a degradation signal whose main determinant is a "destabilizing" N-terminal residue of a protein. Specific N-degrons, discovered in 1986, were the first identified degradation signals in short-lived intracellular proteins. These N-degrons are recognized by a ubiquitin-dependent proteolytic system called the Arg/N-degron pathway. Although bacteria lack the ubiquitin system, they also have N-degron pathways. Studies after 1986 have shown that all 20 amino acids of the genetic code can act, in specific sequence contexts, as destabilizing N-terminal residues. Eukaryotic proteins are targeted for the conditional or constitutive degradation by at least five N-degron systems that differ both functionally and mechanistically: the Arg/N-degron pathway, the Ac/N-degron pathway, the Pro/N-degron pathway, the fMet/N-degron pathway, and the newly named, in this perspective, GASTC/N-degron pathway (GASTC = Gly, Ala, Ser, Thr, Cys). I discuss these systems and the expanded terminology that now encompasses the entire gamut of known N-degron pathways.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11441550PMC
http://dx.doi.org/10.1073/pnas.2408697121DOI Listing

Publication Analysis

Top Keywords

n-degron pathways
12
arg/n-degron pathway
8
pathway
6
n-degron
5
pathways n-degron
4
n-degron degradation
4
degradation signal
4
signal main
4
main determinant
4
determinant "destabilizing"
4

Similar Publications

APC/C-mediated ubiquitylation of extranucleosomal histone complexes lacking canonical degrons.

Nat Commun

March 2025

Division of Chemical Biology and Medicinal Chemistry and Center for Integrated Chemical Biology and Drug Discovery, UNC Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC, USA.

Non-degradative histone ubiquitylation plays a myriad of well-defined roles in the regulation of gene expression and choreographing DNA damage repair pathways. In contrast, the contributions of degradative histone ubiquitylation on genomic processes has remained elusive. Recently, the APC/C has been shown to ubiquitylate histones to regulate gene expression in pluripotent cells, but the molecular mechanism is unclear.

View Article and Find Full Text PDF

3D Histology visualizing hypoxia-induced upregulation of N-terminal cysteine using de novo fluorophore generation.

Redox Biol

March 2025

Department of Chemistry, Seoul National University, Seoul, 08826, South Korea; School of Transdisciplinary Innovations, Seoul National University, Seoul, 08826, South Korea. Electronic address:

Our research group developed a novel fluorescence staining strategy based on the DNFC targeting N-Cys in proteins. By treating biological samples with non-fluorogenic citrate and coupling reagents, we achieved strong cyan fluorescence, enabling effective visualization of N-Cys proteins in cells and tissues. The DNFC reaction occurs specifically on N-Cys residues, making it highly ideal for monitoring protein processing events, particularly within the Arg/N-degron pathway.

View Article and Find Full Text PDF

Substrate Recognition and Cleavage-Site Preferences of Lon Protease.

J Biol Chem

February 2025

Department of Biochemistry and Cell Biology, Center for Infectious Diseases, Graduate Program in Molecular and Cellular Biology, Stony Brook University, Stony Brook, New York 11794. Electronic address:

The evolutionarily conserved AAA+ Lon protease plays a pivotal role in protein homeostasis by precisely remodeling the proteome and specifically removing unfolded, damaged, and surplus natively folded regulatory proteins. Proteolysis by Lon comprises the three fundamental stages of substrate recognition via specific amino acid sequence motifs (degrons), ATP-fueled substrate unfolding and translocation into a sequestered proteolytic chamber, and cleavage of the translocated polypeptide by the peptidase domain. Although a plethora of Lon substrates have been identified in several bacterial species, broadly applicable rules that govern recognition of numerous substrates, and hence the ability to de novo identify new Lon substrates and regulatory pathways, has lagged behind.

View Article and Find Full Text PDF

LZTS3 represses tumorigenesis and radioresistance via CK1δ and β-TrCP-mediated ubiquitination pathway in lung cancer.

Cell Signal

May 2025

Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People's Hospital(Affiliated People's Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, China. Electronic address:

Radioresistance is one of the main causes for local treatment failure in lung cancer. Nevertheless, the potential mechanisms of radioresistance in lung cancer have not been elucidated completely. Here, we discover a carcinoma-inhibiting protein called leucine zipper tumor suppressor 3 (LZTS3), which is low-expressed and related to adverse outcome in lung cancer.

View Article and Find Full Text PDF

One way cells control the speed and specificity of protein degradation is by regulating the activity of ubiquitin ligases. Upon proteotoxic stress in yeast, the intrinsically disordered protein Roq1 binds the ubiquitin ligase Ubr1 as a pseudosubstrate, thereby modulating the degradation of substrates of the N-degron pathway and promoting the elimination of misfolded proteins. The mechanism underlying this reprograming of Ubr1 is unknown.

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!