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Wdr59 promotes or inhibits TORC1 activity depending on cellular context.
Zhang Y, Ting CY, Yang S, Reich J, Fru K, Lilly MA. Zhang Y, et al. Proc Natl Acad Sci U S A. 2023 Jan 3;120(1):e2212330120. doi: 10.1073/pnas.2212330120. Epub 2022 Dec 28. Proc Natl Acad Sci U S A. 2023. PMID: 36577058 Free PMC article.
Conversely, in the Drosophila fat body, Wdr59 promotes the accumulation of the GATOR2 component Mio and is required for TORC1 activation. Similarly, in mammalian HeLa cells, Wdr59 prevents the proteolytic destruction of GATOR2 proteins Mio and Wdr24. ...
Conversely, in the Drosophila fat body, Wdr59 promotes the accumulation of the GATOR2 component Mio and is required for TORC1 activat …
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, …
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 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 …
The landscape of genetic diseases in Saudi Arabia based on the first 1000 diagnostic panels and exomes.
Monies D, Abouelhoda M, AlSayed M, Alhassnan Z, Alotaibi M, Kayyali H, Al-Owain M, Shah A, Rahbeeni Z, Al-Muhaizea MA, Alzaidan HI, Cupler E, Bohlega S, Faqeih E, Faden M, Alyounes B, Jaroudi D, Goljan E, Elbardisy H, Akilan A, Albar R, Aldhalaan H, Gulab S, Chedrawi A, Al Saud BK, Kurdi W, Makhseed N, Alqasim T, El Khashab HY, Al-Mousa H, Alhashem A, Kanaan I, Algoufi T, Alsaleem K, Basha TA, Al-Murshedi F, Khan S, Al-Kindy A, Alnemer M, Al-Hajjar S, Alyamani S, Aldhekri H, Al-Mehaidib A, Arnaout R, Dabbagh O, Shagrani M, Broering D, Tulbah M, Alqassmi A, Almugbel M, AlQuaiz M, Alsaman A, Al-Thihli K, Sulaiman RA, Al-Dekhail W, Alsaegh A, Bashiri FA, Qari A, Alhomadi S, Alkuraya H, Alsebayel M, Hamad MH, Szonyi L, Abaalkhail F, Al-Mayouf SM, Almojalli H, Alqadi KS, Elsiesy H, Shuaib TM, Seidahmed MZ, Abosoudah I, Akleh H, AlGhonaium A, Alkharfy TM, Al Mutairi F, Eyaid W, Alshanbary A, Sheikh FR, Alsohaibani FI, Alsonbul A, Al Tala S, Balkhy S, Bassiouni R, Alenizi AS, Hussein MH, Hassan S, Khalil M, Tabarki B, Alshahwan S, Oshi A, Sabr Y, Alsaadoun S, Salih MA, Mohamed S, Sultana H, Tamim A, El-Haj M, Alshahrani S, Bubshait DK, Alfadhel M, Faquih T, El-Kalioby M, Subhani S, Shah … See abstract for full author list ➔ Monies D, et al. Hum Genet. 2017 Aug;136(8):921-939. doi: 10.1007/s00439-017-1821-8. Epub 2017 Jun 9. Hum Genet. 2017. PMID: 28600779 Free PMC article.
Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CABP1, CCDC186, CCP110, CLSTN2, CNTN3, CNTN5, CTNNA2, CWC22, DMAP1, DMKN, DMXL1, DSCAM, DVL2, ECI1, EP400, EPB41L5, FBXL22, GAP43, GEMIN7, GIT …
Finally, we have encountered candidate variants in 75 genes (ABHD6, ACY3, ADGRB2, ADGRG7, AGTPBP1, AHNAK2, AKAP6, ASB3, ATXN1L, C17orf62, CA …
The FACT complex facilitates expression of lysosomal and antioxidant genes through binding to TFEB and TFE3.
Jeong E, Martina JA, Contreras PS, Lee J, Puertollano R. Jeong E, et al. Autophagy. 2022 Oct;18(10):2333-2349. doi: 10.1080/15548627.2022.2029671. Epub 2022 Mar 1. Autophagy. 2022. PMID: 35230915 Free PMC article.
Together, our data show that chromatin remodeling at the promoter of stress-responsive genes by FACT is important for efficient expression of TFEB and TFE3 targets, thus providing a link between environmental changes, chromatin modifications and transcriptional regulation.Abbrevi …
Together, our data show that chromatin remodeling at the promoter of stress-responsive genes by FACT is important for efficient expression o …
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.
Inhibition of GATOR1 subunits (DEPDC5, Nprl2, and Nprl3) makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling, and epistasis analysis shows that GATOR2 nega …
Inhibition of GATOR1 subunits (DEPDC5, Nprl2, and Nprl3) makes mTORC1 signaling resistant to amino acid deprivation. In contrast, inhibition …
Exome sequencing identifies genes associated with sleep-related traits.
Fei CJ, Li ZY, Ning J, Yang L, Wu BS, Kang JJ, Liu WS, He XY, You J, Chen SD, Yu H, Huang ZL, Feng JF, Yu JT, Cheng W. Fei CJ, et al. Nat Hum Behav. 2024 Jan 4. doi: 10.1038/s41562-023-01785-5. Online ahead of print. Nat Hum Behav. 2024. PMID: 38177695
We identified 22 new genes associated with chronotype (ADGRL4, COL6A3, CLK4 and KRTAP3-3), daytime sleepiness (ST3GAL1 and ANKRD12), daytime napping (PLEKHM1, ANKRD12 and ZBTB21), snoring (WDR59) and sleep apnoea (13 genes). Notably, 20 of these genes were confirmed to be …
We identified 22 new genes associated with chronotype (ADGRL4, COL6A3, CLK4 and KRTAP3-3), daytime sleepiness (ST3GAL1 and ANKRD12), daytime …
A Transcriptome-Wide Association Study Identifies Novel Candidate Susceptibility Genes for Pancreatic Cancer.
Zhong J, Jermusyk A, Wu L, Hoskins JW, Collins I, Mocci E, Zhang M, Song L, Chung CC, Zhang T, Xiao W, Albanes D, Andreotti G, Arslan AA, Babic A, Bamlet WR, Beane-Freeman L, Berndt S, Borgida A, Bracci PM, Brais L, Brennan P, Bueno-de-Mesquita B, Buring J, Canzian F, Childs EJ, Cotterchio M, Du M, Duell EJ, Fuchs C, Gallinger S, Gaziano JM, Giles GG, Giovannucci E, Goggins M, Goodman GE, Goodman PJ, Haiman C, Hartge P, Hasan M, Helzlsouer KJ, Holly EA, Klein EA, Kogevinas M, Kurtz RJ, LeMarchand L, Malats N, Männistö S, Milne R, Neale RE, Ng K, Obazee O, Oberg AL, Orlow I, Patel AV, Peters U, Porta M, Rothman N, Scelo G, Sesso HD, Severi G, Sieri S, Silverman D, Sund M, Tjønneland A, Thornquist MD, Tobias GS, Trichopoulou A, Van Den Eeden SK, Visvanathan K, Wactawski-Wende J, Wentzensen N, White E, Yu H, Yuan C, Zeleniuch-Jacquotte A, Hoover R, Brown K, Kooperberg C, Risch HA, Jacobs EJ, Li D, Yu K, Shu XO, Chanock SJ, Wolpin BM, Stolzenberg-Solomon RZ, Chatterjee N, Klein AP, Smith JP, Kraft P, Shi J, Petersen GM, Zheng W, Amundadottir LT. Zhong J, et al. J Natl Cancer Inst. 2020 Oct 1;112(10):1003-1012. doi: 10.1093/jnci/djz246. J Natl Cancer Inst. 2020. PMID: 31917448 Free PMC article.

RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80

RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer ris …
SZT2 dictates GATOR control of mTORC1 signalling.
Peng M, Yin N, Li MO. Peng M, et al. Nature. 2017 Mar 16;543(7645):433-437. doi: 10.1038/nature21378. Epub 2017 Feb 15. Nature. 2017. PMID: 28199315 Free PMC article.
Hyperactivation of mTORC1 in SZT2-deficient cells could be partially corrected by overexpression of the GATOR1 component DEPDC5, and by the lysosome-targeted GATOR2 component WDR59 or lysosome-targeted SESN2. These findings demonstrate that SZT2 has a central role in dicta …
Hyperactivation of mTORC1 in SZT2-deficient cells could be partially corrected by overexpression of the GATOR1 component DEPDC5, and by the …
Author Correction: SZT2 dictates GATOR control of mTORC1 signalling.
Peng M, Yin N, Li MO. Peng M, et al. Nature. 2018 Jun;558(7710):E2. doi: 10.1038/s41586-018-0114-2. Nature. 2018. PMID: 29769712
(In the uncropped blot for Extended Data Fig. 7e, the actin bands were mislabelled as 'WDR59' and this led to the error.) Extended Data Fig. 7 and the Supplementary Information of the original Letter have been corrected online. ...
(In the uncropped blot for Extended Data Fig. 7e, the actin bands were mislabelled as 'WDR59' and this led to the error.) Extended Da …
19 results