| 2013 |
WDR24 is a subunit of the GATOR2 complex (along with Mios, WDR59, Seh1L, and Sec13), which positively regulates mTORC1 signaling upstream of the Rag GTPases. Inhibition of WDR24/GATOR2 suppresses mTORC1 signaling, and epistasis analysis shows GATOR2 negatively regulates GATOR1 (DEPDC5/Nprl2/Nprl3), which itself has GAP activity toward RagA/RagB. |
RNAi knockdown, epistasis analysis, Co-immunoprecipitation, mTORC1 activity assays (phospho-S6K1) |
Science |
High |
23723238
|
| 2022 |
Cryo-EM structure of human GATOR2 revealed a ~1.1 MDa two-fold symmetric cage-like architecture with an octagonal scaffold containing two WDR24, four MIOS, and two WDR59 subunits circularized via non-catalytic RING domains and α-solenoids. WDR24 contributes WD40 β-propeller dimers that mediate interactions with SESN2, CASTOR1, and GATOR1. SEH1L and SEC13 stabilize the complex via β-propeller blade donation. |
Cryo-electron microscopy, biochemical reconstitution |
Nature |
High |
35831510
|
| 2016 |
Drosophila Wdr24 (ortholog of WDR24) is required for robust TORC1 activation and cellular growth in vivo. Additionally, Wdr24 has a TORC1-independent function in regulating lysosome dynamics and autophagic flux. In wdr24-/- knockout HeLa cells, Wdr24 promotes lysosome acidification and autophagic flux. |
Null allele characterization, genetic epistasis with GATOR1 components, biochemical fractionation, cell biological assays, HeLa knockout cell line |
PLoS genetics |
High |
27166823
|
| 2020 |
WDR24 is the GATOR2 component essential for the Sestrin2-GATOR2 interaction. Deleting or silencing WDR24 completely ablates Sestrin2-induced AKT activation. WDR24 bridges Sestrin2 to the GATOR2 complex, which in turn interacts with mTORC2 through WDR59 to induce AKT activation. |
Co-immunoprecipitation, siRNA knockdown, WDR24 deletion, in vitro kinase assay, AKT activation assays |
The Journal of biological chemistry |
High |
31915252
|
| 2023 |
AMPK directly phosphorylates WDR24 at Ser155 upon glucose deprivation, disrupting the integrity of the GATOR2 complex and suppressing mTORC1 activation. Phosphomimetic Wdr24-S155D knock-in mice exhibit early embryonic lethality and reduced mTORC1 activity, while phospho-deficient Wdr24-S155A knock-in mice are more resistant to fasting and display elevated mTORC1 activity. |
In vitro kinase assay, phosphomimetic and phospho-deficient knock-in mice, Co-immunoprecipitation, mTORC1 activity assays |
Nature metabolism |
High |
36732624
|
| 2023 |
PRMT1, activated by CDK5-mediated phosphorylation at S307 in response to amino acids, translocates from nucleus to cytoplasm/lysosome and methylates WDR24, an essential GATOR2 component, to activate the mTORC1 pathway. Disruption of the CDK5-PRMT1-WDR24 axis suppresses mTORC1 signaling, HCC cell proliferation, and xenograft tumor growth. |
Co-immunoprecipitation, arginine methylation assays, subcellular fractionation/localization, siRNA knockdown, xenograft tumor models |
Cell reports |
Medium |
36995937
|
| 2023 |
ILF3 tethers the GATOR complexes (including WDR24-containing GATOR2) to lysosomes to control mTORC1. Adding a lysosome-targeting sequence to WDR24 directly bypasses the requirement for ILF3 in amino-acid-dependent mTORC1 signalling, demonstrating that lysosomal localization of GATOR2 via WDR24 is functionally sufficient. |
Genome-wide CRISPR/Cas9 screen, lysosome-targeting sequence rescue experiment, mTORC1 activity assays (pS6 FACS) |
Nature cell biology |
Medium |
37037994
|
| 2025 |
Cryo-EM structures of GATOR2 bound to Sestrin2 or CASTOR1 revealed that Sestrin2 interacts with the WDR24-Seh1L subcomplex, inducing conformational changes, while CASTOR1 engages Mios WD40 β-propellers. Binding of either sensor restricts the dynamic WDR24 β-propeller, a domain essential for nutrient-dependent mTORC1 activation. Amino acid binding triggers structural rearrangements in sensors that cause their dissociation from GATOR2. |
Cryo-electron microscopy, site-directed mutagenesis of binding interfaces, functional mTORC1 signaling assays |
Nature |
High |
40836086
|
| 2025 |
Cryo-EM structures of GATOR2 in three inhibitory states (CASTOR1-bound, Sestrin2-bound, dual-bound) confirmed that Sestrin2 interacts with the WDR24-Seh1L subcomplex while CASTOR1 engages Mios WD40 β-propellers. HDX-MS revealed dynamic motions in apo-GATOR2 and its sensor complexes. |
Cryo-electron microscopy, hydrogen-deuterium exchange mass spectrometry (HDX-MS) |
Cell reports |
High |
40742811
|
| 2024 |
D-serine produced by Mycobacterium tuberculosis interacts with WDR24 and inhibits mTORC1 activation in CD8+ T cells, decreasing T-bet expression and reducing IFN-γ production. |
Metabolomic, proteomic and genetic approaches; direct interaction assay between D-serine and WDR24; mTORC1 activity assays in CD8+ T cells |
Nature microbiology |
Medium |
38806671
|
| 2022 |
In mammalian HeLa cells, Wdr59 (another GATOR2 component) prevents the proteolytic destruction of GATOR2 proteins Mio and Wdr24. In Wdr59 knockout HeLa cells, reduced Wdr24 protein levels correlated with reduced TORC1 activity, which was restored along with Wdr24 levels upon proteasome inhibition. |
Wdr59 knockout HeLa cells, proteasome inhibition rescue, immunoblot for Wdr24 protein levels, mTORC1 activity assays |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
36577058
|
| 2025 |
Radiation-induced AMPK activation phosphorylates WDR24, which promotes NPRL2 dissociation from the GATOR1 complex and facilitates NPRL2 nuclear translocation. Nuclear NPRL2 then inactivates E3 ubiquitin ligases HERC2 and RNF8 to enhance DNA repair. AMPK inhibition blocks this cascade, impairing DNA repair and radiosensitizing CRC cells. |
Co-immunoprecipitation, nuclear fractionation, AMPK inhibition, in vitro and in vivo radiosensitization assays |
Acta pharmaceutica Sinica. B |
Medium |
41584340
|