Last update 01 Nov 2024

MIOS

Last update 01 Nov 2024

Basic Info

Synonyms

FLJ20323, GATOR complex protein MIOS, meiosis regulator for oocyte development

+ [5]

Introduction

As a component of the GATOR subcomplex GATOR2, functions within the amino acid-sensing branch of the TORC1 signaling pathway. Indirectly activates mTORC1 and the TORC1 signaling pathway through the inhibition of the GATOR1 subcomplex (PubMed:23723238). It is negatively regulated by the upstream amino acid sensors SESN2 and CASTOR1 (PubMed:25457612, PubMed:27487210).

Drugs associated with MIOS

Tanshinone IIA

Target

CES x MIOS

Mechanism

CES inhibitors [+1]

Active Org.

Royal Holloway University of London [+2]

Originator Org.

Changhua Christian Hospital

Active Indication

Glioblastoma [+3]

Inactive Indication-

Drug Highest PhasePreclinical

First Approval Ctry. / Loc.-

First Approval Date20 Jan 1800

100 Clinical Results associated with MIOS

100 Translational Medicine associated with MIOS

0 Patents (Medical) associated with MIOS

Literatures (Medical) associated with MIOS

29 Mar 2024·Bioscience Reports

New insights into GATOR2-dependent interactions and its conformational changes in amino acid sensing

Article

Author: Wu, Geng ; Sun, Xuan ; Yang, Can

AbstractEukaryotic cells coordinate growth under different environmental conditions via mechanistic target of rapamycin complex 1 (mTORC1). In the amino-acid-sensing signalling pathway, the GATOR2 complex, containing five evolutionarily conserved subunits (WDR59, Mios, WDR24, Seh1L and Sec13), is required to regulate mTORC1 activity by interacting with upstream CASTOR1 (arginine sensor) and Sestrin2 (leucine sensor and downstream GATOR1 complex). GATOR2 complex utilizes β-propellers to engage with CASTOR1, Sestrin2 and GATOR1, removal of these β-propellers results in substantial loss of mTORC1 capacity. However, structural information regarding the interface between amino acid sensors and GATOR2 remains elusive. With the recent progress of the AI-based tool AlphaFold2 (AF2) for protein structure prediction, structural models were predicted for Sentrin2-WDR24-Seh1L and CASTOR1-Mios β-propeller. Furthermore, the effectiveness of relevant residues within the interface was examined using biochemical experiments combined with molecular dynamics (MD) simulations. Notably, fluorescence resonance energy transfer (FRET) analysis detected the structural transition of GATOR2 in response to amino acid signals, and the deletion of Mios β-propeller severely impeded that change at distinct arginine levels. These findings provide structural perspectives on the association between GATOR2 and amino acid sensors and can facilitate future research on structure determination and function.

01 Jan 2023·Molecular Cell

Ring domains are essential for GATOR2-dependent mTORC1 activation

Article

Author: Liu, Songlei ; Dai, Xiaoming ; Inuzuka, Hiroyuki ; Zhang, Tao ; Zhou, Hongfei ; Xiao, Jianru ; Wang, Ping ; Jiang, Cong ; Fu, Tianmin ; He, Shaohui ; Guo, Jianping ; Li, Dali ; Yu, Haihong ; Fang, Lan ; Wei, Wenyi ; Pan, Weijuan

The GATOR2-GATOR1 signaling axis is essential for amino-acid-dependent mTORC1 activation. However, the molecular function of the GATOR2 complex remains unknown. Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 integrity, disruption of which leads to self-ubiquitination of WDR24. Physiologically, leucine stimulation dissociates Sestrin2 from the Ring domain of WDR24 and confers its availability to UBE2D3 and subsequent ubiquitination of NPRL2, contributing to GATOR2-mediated GATOR1 inactivation. As such, WDR24 ablation or Ring deletion prevents mTORC1 activation, leading to severe growth defects and embryonic lethality at E10.5 in mice. Hence, our findings demonstrate that Ring domains are essential for GATOR2 to transmit amino acid availability to mTORC1 and further reveal the essentiality of nutrient sensing during embryonic development.

01 Oct 2022·Microbiological Research

Genetic mapping of a bioethanol yeast strain reveals new targets for hydroxymethylfurfural- and thermotolerance

Article

Author: Maneira, Carla ; de Mello, Fellipe da Silveira Bezerra ; Coradini, Alessandro Luis Venega ; Teixeira, Gleidson Silva ; Pereira, Gonçalo Amarante Guimarães ; Furlan, Monique ; Carazzolle, Marcelo Falsarella

Current technology that enables bioethanol production from agricultural biomass imposes harsh conditions for Saccharomyces cerevisiae's metabolism. In this work, the genetic architecture of industrial bioethanol yeast strain SA-1 was evaluated. SA-1 segregant FMY097 was previously described as highly aldehyde resistant and here also as thermotolerant: two important traits for the second-generation industry. A Quantitative Trait Loci (QTL) mapping of 5-hydroxymethylfurfural (HMF) -resistant segregants of hybrid FMY097/BY4742 disclosed a region in chromosome II bearing alleles with uncommon non-synonymous (NS) single nucleotide polymorphisms (SNPs) in FMY097: MIX23, PKC1, SEA4, and SRO77. Allele swap to susceptible laboratory strain BY4742 revealed that SEA4^FMY097 enhances robustness towards HMF, but the industrial fitness could not be fully recovered. The genetic network arising from the causative genes in the QTL window suggests that intracellular signaling TOR (Target of Rapamycin) and CWI (Cell Wall Integrity) pathways are regulators of this phenotype in FMY097. Because the QTL mapping did not result in one major allelic contribution to the evaluated trait, a background effect in FMY097's HMF resistance is expected. Quantification of NADPH - cofactor implied in endogenous aldehyde detoxification reactions - supports the former hypothesis, given its high availability in FMY097. Regarding thermotolerance, SEA4^FMY097 grants BY4742 ability to grow in temperatures as high as 38 ºC in liquid, while allele PKC1^FMY097 allows growth up to 40 ºC in solid medium. Both SEA4^FMY097 and PKC1^FMY097 encode rare NS SNPs, not found in other > 1013S. cerevisiae. Altogether, these findings point towards crucial membrane and stress mediators for yeast robustness.

Analysis

Perform a panoramic analysis of this field.

view full example data

Chat with Hiro

Get started for free today!

Accelerate Strategic R&D decision making with Synapse, PatSnap’s AI-powered Connected Innovation Intelligence Platform Built for Life Sciences Professionals.

Start your data trial now!

Synapse data is also accessible to external entities via APIs or data packages. Empower better decisions with the latest in pharmaceutical intelligence.

Bio

Bio Sequences Search & Analysis

Chemical

Chemical Structures Search & Analysis

MIOS

Basic Info

Related

Analysis