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Ring domains are essential for GATOR2-dependent mTORC1 activation.
Jiang C, Dai X, He S, Zhou H, Fang L, Guo J, Liu S, Zhang T, Pan W, Yu H, Fu T, Li D, Inuzuka H, Wang P, Xiao J, Wei W. Jiang C, et al. Mol Cell. 2023 Jan 5;83(1):74-89.e9. doi: 10.1016/j.molcel.2022.11.021. Epub 2022 Dec 16. Mol Cell. 2023. PMID: 36528027 Free PMC article.
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 int …
Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation …
AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation.
Dai X, Jiang C, Jiang Q, Fang L, Yu H, Guo J, Yan P, Chi F, Zhang T, Inuzuka H, Asara JM, Wang P, Guo J, Wei W. Dai X, et al. Nat Metab. 2023 Feb;5(2):265-276. doi: 10.1038/s42255-022-00732-4. Epub 2023 Feb 2. Nat Metab. 2023. PMID: 36732624 Free PMC article.
Phosphomimetic Wdr24(S155D) knock-in mice exhibit early embryonic lethality and reduced mTORC1 activity. ...Our findings reveal that AMPK-mediated phosphorylation of WDR24 modulates glucose-induced mTORC1 activation, thereby providing a rationale for targeting AMPK- …
Phosphomimetic Wdr24(S155D) knock-in mice exhibit early embryonic lethality and reduced mTORC1 activity. ...Our findings reveal that …
Dysregulated Amino Acid Sensing Drives Colorectal Cancer Growth and Metabolic Reprogramming Leading to Chemoresistance.
Solanki S, Sanchez K, Ponnusamy V, Kota V, Bell HN, Cho CS, Kowalsky AH, Green M, Lee JH, Shah YM. Solanki S, et al. Gastroenterology. 2023 Mar;164(3):376-391.e13. doi: 10.1053/j.gastro.2022.11.014. Epub 2022 Nov 18. Gastroenterology. 2023. PMID: 36410445 Free PMC article.
BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. ...We found amino acid-sensing pathways to be essential in the cellular reprogramming of chemoresistance, and chemotherapeutic-resistant patients with col …
BACKGROUND & AIMS: Colorectal cancer (CRC) is a devastating disease that is highly modulated by dietary nutrients. ...We found am …
CDK5-PRMT1-WDR24 signaling cascade promotes mTORC1 signaling and tumor growth.
Yin S, Liu L, Ball LE, Wang Y, Bedford MT, Duncan SA, Wang H, Gan W. Yin S, et al. Cell Rep. 2023 Apr 25;42(4):112316. doi: 10.1016/j.celrep.2023.112316. Epub 2023 Mar 29. Cell Rep. 2023. PMID: 36995937 Free PMC article.
Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation and xenograft tumor growth. ...Thus, our study dissects a phosphorylation- and arginine methylation-dependent regulatory mechanism of mTORC1 activation and tumor growth and …
Disruption of the CDK5-PRMT1-WDR24 axis suppresses hepatocellular carcinoma (HCC) cell proliferation and xenograft tumor growth. ...T …
Structure of the nutrient-sensing hub GATOR2.
Valenstein ML, Rogala KB, Lalgudi PV, Brignole EJ, Gu X, Saxton RA, Chantranupong L, Kolibius J, Quast JP, Sabatini DM. Valenstein ML, et al. Nature. 2022 Jul;607(7919):610-616. doi: 10.1038/s41586-022-04939-z. Epub 2022 Jul 13. Nature. 2022. PMID: 35831510 Free PMC article.
Amino acids signal to mTORC1 through the Rag GTPases, which are regulated by several protein complexes, including GATOR1 and GATOR2. GATOR2, which has five components (WDR24, MIOS, WDR59, SEH1L and SEC13), is required for amino acids to activate mTORC1 and interacts with t …
Amino acids signal to mTORC1 through the Rag GTPases, which are regulated by several protein complexes, including GATOR1 and GATOR2. GATOR2, …
Sestrin2 is a leucine sensor for the mTORC1 pathway.
Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM. Wolfson RL, et al. Science. 2016 Jan 1;351(6268):43-8. doi: 10.1126/science.aab2674. Epub 2015 Oct 8. Science. 2016. PMID: 26449471 Free PMC article.
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. Bar-Peled L, et al. Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044. Science. 2013. PMID: 23723238 Free PMC article.
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer. In cancer cells with inactivating mutations in GATOR1, mTORC1 is hyperactive and insensitive to amino acid starvation, and such cells are hypersens …
GATOR1 has GTPase-activating protein (GAP) activity for RagA and RagB, and its components are mutated in human cancer. In cancer …
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function.
Cai W, Wei Y, Jarnik M, Reich J, Lilly MA. Cai W, et al. PLoS Genet. 2016 May 11;12(5):e1006036. doi: 10.1371/journal.pgen.1006036. eCollection 2016 May. PLoS Genet. 2016. PMID: 27166823 Free PMC article.
Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. ...Consistent with our findings in Dr …
Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has …
Identification of Epigenetically Regulated Genes Distinguishing Intracranial from Extracranial Melanoma Metastases.
Westphal D, Meinhardt M, Grützmann K, Schöne L, Steininger J, Neuhaus LT, Wiegel M, Schrimpf D, Aust DE, Schröck E, Baretton GB, Beissert S, Juratli TA, Schackert GG, Gravemeyer J, Becker JC, von Deimling A, Koelsche C, Klink B, Meier F, Schulz A, Muders MH, Seifert M. Westphal D, et al. J Invest Dermatol. 2023 Jul;143(7):1233-1245.e17. doi: 10.1016/j.jid.2023.01.011. Epub 2023 Jan 28. J Invest Dermatol. 2023. PMID: 36716920 Free article.
In accordance with the underlying promoter methylation and gene expression changes, a significantly different protein expression was confirmed for STK10, PDXK, WDR24, CSSP1, NMB, RASL11B, phosphorylated PRKCZ, PRKCZ, and phosphorylated GRB10 in the intracranial metastases. …
In accordance with the underlying promoter methylation and gene expression changes, a significantly different protein expression was confirm …
Pre-clinical activity of combined LSD1 and mTORC1 inhibition in MLL-translocated acute myeloid leukaemia.
Deb G, Wingelhofer B, Amaral FMR, Maiques-Diaz A, Chadwick JA, Spencer GJ, Williams EL, Leong HS, Maes T, Somervaille TCP. Deb G, et al. Leukemia. 2020 May;34(5):1266-1277. doi: 10.1038/s41375-019-0659-6. Epub 2019 Nov 28. Leukemia. 2020. PMID: 31780813 Free PMC article.
We identified multiple components of the amino acid sensing arm of mTORC1 signalling-RRAGA, MLST8, WDR24 and LAMTOR2-as cellular sensitizers to LSD1 inhibition. Knockdown of mTORC1 components, or mTORC1 pharmacologic inhibition, in combination with LSD1 inhibition enhanced …
We identified multiple components of the amino acid sensing arm of mTORC1 signalling-RRAGA, MLST8, WDR24 and LAMTOR2-as cellular sens …
11 results