Amino acids regulate TOR complex 1 (TORC1) via two counteracting mechanisms, one activating and one inactivating. The presence of amino acids causes TORC1 recruitment to lysosomes where TORC1 is activated by binding Rheb. How the absence of amino acids inactivates TORC1 is less well understood. Amino acid starvation recruits the TSC1/TSC2 complex to the vicinity of TORC1 to inhibit Rheb; however, the upstream mechanisms regulating TSC2 are not known. We identify here the eIF4A-containing eIF4F translation initiation complex as an upstream regulator of TSC2 in response to amino acid withdrawal in Drosophila We find that TORC1 and translation preinitiation complexes bind each other. Cells lacking eIF4F components retain elevated TORC1 activity upon amino acid removal. This effect is specific for eIF4F and not a general consequence of blocked translation. This study identifies specific components of the translation machinery as important mediators of TORC1 inactivation upon amino acid removal.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4868951 | PMC |
| http://dx.doi.org/10.15252/embj.201593118 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Tubulin detyrosination shapes cytoskeletal architecture and virulence.
Proc Natl Acad Sci U S A
January 2025
Maladies infectieuses et Vecteurs: Ecologie, Génétique, Evolution et Contrôle, University of Montpellier, CNRS, Institut de Recherche pour le Développement, Montpellier 34095, France.
Tubulin detyrosination has been implicated in various human disorders and is important for regulating microtubule dynamics. While in most organisms this modification is restricted to α-tubulin, in trypanosomatid parasites, it occurs on both α- and β-tubulin. Here, we show that in , a single vasohibin (LmVASH) enzyme is responsible for differential kinetics of α- and β-tubulin detyrosination.
View Article and Find Full Text PDFGlyphosate exposure and GM seed rollout unequally reduced perinatal health.
Proc Natl Acad Sci U S A
January 2025
Department of Economics, University of Oregon, Eugene, OR 97403.
The advent of herbicide-tolerant genetically modified (GM) crops spurred rapid and widespread use of the herbicide glyphosate throughout US agriculture. In the two decades following GM-seeds' introduction, the volume of glyphosate applied in the United States increased by more than 750%. Despite this breadth and scale, science and policy remain unresolved regarding the effects of glyphosate on human health.
View Article and Find Full Text PDFContext-Dependent Heterotypic Assemblies of Intrinsically Disordered Peptides.
J Am Chem Soc
January 2025
Department of Chemistry, Brandeis University, 415 South St., Waltham, Massachusetts 02454, United States.
Despite their critical role in context-dependent interactions for protein functions, intrinsically disordered regions (IDRs) are often overlooked for designing peptide assemblies. Here, we exploit IDRs to enable context-dependent heterotypic assemblies of intrinsically disordered peptides, where "context-dependent" refers to assembly behavior driven by interactions with other molecules. By attaching an aromatic segment to oppositely charged intrinsically disordered peptides, we achieve a nanofiber formation.
View Article and Find Full Text PDFEstablishing an animal model for post-inflammatory hyperpigmentation following fractional CO laser application.
Lasers Med Sci
January 2025
Hangzhou Third People's Hospital, Hangzhou, China.
Background: Post-inflammatory hyperpigmentation (PIH) is a common cosmetic concern, often leading to significant psychological distress for the patients. With the widespread application of lasers including ablative fractional resurfacing (AFR) with a 10,600 nm CO laser, PIH caused by lasers is becoming increasingly common. But due to the absence of an appropriate animal research model, our understanding of pathophysiological mechanisms and preventive strategies for PIH remains limited.
View Article and Find Full Text PDFCharacterization and design of dipeptide media formulation for scalable therapeutic production.
Appl Microbiol Biotechnol
January 2025
School of Chemical Engineering, Sungkyunkwan University, 2066 Seobu-Ro, Jangan-GuGyeonggi-Do 16419, Suwon-Si, South Korea.
Process intensification and simplification in biopharmaceutical manufacturing have driven the exploration of advanced feeding strategies to improve culture performance and process consistency. Conventional media design strategies, however, are often constrained by the stability and solubility challenges of amino acids, particularly in large-scale applications. As a result, dipeptides have emerged as promising alternatives.
View Article and Find Full Text PDFWant 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!