Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61388963%3A_____%2F25%3A00605347" target="_blank" >RIV/61388963:_____/25:00605347 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1038/s41586-024-07974-0" target="_blank" >https://doi.org/10.1038/s41586-024-07974-0</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1038/s41586-024-07974-0" target="_blank" >10.1038/s41586-024-07974-0</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation

Popis výsledku v původním jazyce

Activation of the mechanistic target of rapamycin complex 1 (mTORC1) requires its nutrient-dependent recruitment to the surface of the lysosome, a process that is controlled by several multiprotein complexes, including GATOR1, a negative regulator of mTORC1 signalling. Recently, Chen et al. suggested that KLHL22-dependent ubiquitylation and proteasomal degradation of the GATOR1 component DEPDC5 mediates mTORC1 activation by amino acids. Here we report that the antibody central to the conclusions of Chen et al. neither sensitively nor specifically detects endogenous DEPDC5, and we determine, using validated antibodies and endogenously tagged cell lines, that the stability of DEPDC5 is insensitive to amino acid availability, proteasome activity and KLHL22 loss of function. These results call into question the conclusions of Chen et al. and indicate that alternative mechanisms convey nutrient availability to mTORC1.

Název v anglickém jazyce

Amino acids and KLHL22 do not activate mTORC1 via DEPDC5 degradation

Popis výsledku anglicky

Activation of the mechanistic target of rapamycin complex 1 (mTORC1) requires its nutrient-dependent recruitment to the surface of the lysosome, a process that is controlled by several multiprotein complexes, including GATOR1, a negative regulator of mTORC1 signalling. Recently, Chen et al. suggested that KLHL22-dependent ubiquitylation and proteasomal degradation of the GATOR1 component DEPDC5 mediates mTORC1 activation by amino acids. Here we report that the antibody central to the conclusions of Chen et al. neither sensitively nor specifically detects endogenous DEPDC5, and we determine, using validated antibodies and endogenously tagged cell lines, that the stability of DEPDC5 is insensitive to amino acid availability, proteasome activity and KLHL22 loss of function. These results call into question the conclusions of Chen et al. and indicate that alternative mechanisms convey nutrient availability to mTORC1.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10608 - Biochemistry and molecular biology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2025

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Nature

ISSN

0028-0836

e-ISSN

1476-4687

Svazek periodika

637

Číslo periodika v rámci svazku

8045

Stát vydavatele periodika

GB - Spojené království Velké Británie a Severního Irska

Počet stran výsledku

4

Strana od-do

"E11"-"E14"

Kód UT WoS článku

001410545800001

EID výsledku v databázi Scopus

2-s2.0-85215071300