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GIGYF1 disruption associates with autism and impaired IGF-1R signaling.
Chen G, Yu B, Tan S, Tan J, Jia X, Zhang Q, Zhang X, Jiang Q, Hua Y, Han Y, Luo S, Hoekzema K, Bernier RA, Earl RK, Kurtz-Nelson EC, Idleburg MJ, Madan-Khetarpal S, Clark R, Sebastian J, Fernandez-Jaen A, Alvarez S, King SD, Ramos LL, Santos MLS, Martin DM, Brooks D, Symonds JD, Cutcutache I, Pan Q, Hu Z, Yuan L, Eichler EE, Xia K, Guo H. Chen G, et al. J Clin Invest. 2022 Oct 3;132(19):e159806. doi: 10.1172/JCI159806. J Clin Invest. 2022. PMID: 35917186 Free PMC article.
An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second-most mutated gene among known ASD high-confidence risk genes. ...We showed that GIGYF1 regulated the recycling of IGF-1R to the cell …
An excess of likely gene-disruptive (LGD) mutations in GIGYF1 was implicated in ASD. Here, we report that GIGYF1 is the second …
Genetic Ablation of GIGYF1, Associated With Autism, Causes Behavioral and Neurodevelopmental Defects in Zebrafish and Mice.
Ding Z, Huang G, Wang T, Duan W, Li H, Wang Y, Jia H, Yang Z, Wang K, Chu X, Kurtz-Nelson EC, Ahlers K, Earl RK, Han Y, Feliciano P, Chung WK, Eichler EE, Jiang M, Xiong B. Ding Z, et al. Biol Psychiatry. 2023 Nov 15;94(10):769-779. doi: 10.1016/j.biopsych.2023.02.993. Epub 2023 Mar 15. Biol Psychiatry. 2023. PMID: 36924980 Free PMC article.
Loss of GIGYF1 causes similar behavioral effects in zebrafish and mice, including elevated levels of anxiety and reduced social engagement, which is reminiscent of the behavioral deficits in human patients carrying GIGYF1 variants. Moreover, excitatory neuron-specif …
Loss of GIGYF1 causes similar behavioral effects in zebrafish and mice, including elevated levels of anxiety and reduced social engag …
GIGYF1-disturbed IGF-1R recycling: a potential contributor to autism spectrum disorder pathogenesis?
Xing M, Zhang Q, Song W. Xing M, et al. J Clin Invest. 2022 Oct 3;132(19):e163553. doi: 10.1172/JCI163553. J Clin Invest. 2022. PMID: 36189799 Free PMC article.
GIGYF1-deficiency affected the recycling of IGF-1R, thereby suppressing the IGF-1R/ERK signaling pathway. Disruption of GIGYF1 in the developing mouse brain led to social deficits and cognitive impairments. ...
GIGYF1-deficiency affected the recycling of IGF-1R, thereby suppressing the IGF-1R/ERK signaling pathway. Disruption of GIGYF1 …
Repression of mRNA translation initiation by GIGYF1 via disrupting the eIF3-eIF4G1 interaction.
Choi JH, Luo J, Hesketh GG, Guo S, Pistofidis A, Ladak RJ, An Y, Naeli P, Alain T, Schmeing TM, Gingras AC, Duchaine T, Zhang X, Sonenberg N, Jafarnejad SM. Choi JH, et al. Sci Adv. 2024 Jul 19;10(29):eadl5638. doi: 10.1126/sciadv.adl5638. Epub 2024 Jul 17. Sci Adv. 2024. PMID: 39018414 Free PMC article.
Upon recruitment to a target mRNA, GIGYF1 binds to subunits of eukaryotic translation initiation factor 3 (eIF3) at the eIF3-eIF4G1 interaction interface. This interaction disrupts the eIF3 binding to eIF4G1, resulting in transcript-specific translational repression. Deple …
Upon recruitment to a target mRNA, GIGYF1 binds to subunits of eukaryotic translation initiation factor 3 (eIF3) at the eIF3-eIF4G1 i …
GIGYF1/2-Driven Cooperation between ZNF598 and TTP in Posttranscriptional Regulation of Inflammatory Signaling.
Tollenaere MAX, Tiedje C, Rasmussen S, Nielsen JC, Vind AC, Blasius M, Batth TS, Mailand N, Olsen JV, Gaestel M, Bekker-Jensen S. Tollenaere MAX, et al. Cell Rep. 2019 Mar 26;26(13):3511-3521.e4. doi: 10.1016/j.celrep.2019.03.006. Cell Rep. 2019. PMID: 30917308 Free article.
A key factor in this regulation is tristetraprolin (TTP), an RNA-binding protein (RBP) that recruits RNA-destabilizing factors and the translation inhibitory complex 4EHP-GIGYF1/2 to AU-rich element (ARE)-containing mRNAs. Here, we show that the RBP ZNF598 contributes to t …
A key factor in this regulation is tristetraprolin (TTP), an RNA-binding protein (RBP) that recruits RNA-destabilizing factors and the trans …
4EHP and GIGYF1/2 Mediate Translation-Coupled Messenger RNA Decay.
Weber R, Chung MY, Keskeny C, Zinnall U, Landthaler M, Valkov E, Izaurralde E, Igreja C. Weber R, et al. Cell Rep. 2020 Oct 13;33(2):108262. doi: 10.1016/j.celrep.2020.108262. Cell Rep. 2020. PMID: 33053355 Free PMC article.
However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we show that 4EHP-GIGYF1/2 complexes trigger co-translational mRNA decay. Human cells lacking these proteins accumulate mRNAs with prom …
However, our understanding of the molecular events that coordinate ribosome transit with the mRNA decay machinery is still limited. Here, we …
GIGYF1 loss of function is associated with clonal mosaicism and adverse metabolic health.
Zhao Y, Stankovic S, Koprulu M, Wheeler E, Day FR, Lango Allen H, Kerrison ND, Pietzner M, Loh PR, Wareham NJ, Langenberg C, Ong KK, Perry JRB. Zhao Y, et al. Nat Commun. 2021 Jul 7;12(1):4178. doi: 10.1038/s41467-021-24504-y. Nat Commun. 2021. PMID: 34234147 Free PMC article.
We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not previously been implicated in any complex trait, but here loss-of-function carriers exhibit six-fold higher susceptibility to LOY (OR = 5.99 [3 …
We find that loss of function of two genes-CHEK2 and GIGYF1-reach exome-wide significance. Rare alleles in GIGYF1 have not pre …
Analysis of rare genetic variation underlying cardiometabolic diseases and traits among 200,000 individuals in the UK Biobank.
Jurgens SJ, Choi SH, Morrill VN, Chaffin M, Pirruccello JP, Halford JL, Weng LC, Nauffal V, Roselli C, Hall AW, Oetjens MT, Lagerman B, vanMaanen DP; Regeneron Genetics Center; Aragam KG, Lunetta KL, Haggerty CM, Lubitz SA, Ellinor PT. Jurgens SJ, et al. Nat Genet. 2022 Mar;54(3):240-250. doi: 10.1038/s41588-021-01011-w. Epub 2022 Feb 17. Nat Genet. 2022. PMID: 35177841 Free PMC article.
Many genes showed independent convergence of rare and common variant evidence, including an association between GIGYF1 and type 2 diabetes. We identified several large effect associations for height and 18 unique genes associated with blood lipid or glucose levels. ...
Many genes showed independent convergence of rare and common variant evidence, including an association between GIGYF1 and type 2 dia …
Low Expression of GIGYF1 Inhibits Metastasis, Proliferation, and Promotes Apoptosis and Autophagy of Gastric Cancer Cells.
Zhu L, Yao Z, Luo Q, Liu Y, Zhao W, Shao C, Shao S, Cui F. Zhu L, et al. Int J Med Sci. 2023 Jun 12;20(8):1038-1045. doi: 10.7150/ijms.82719. eCollection 2023. Int J Med Sci. 2023. PMID: 37484805 Free PMC article.
GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. ...Meanwhile, GIGYF1 knockdowns inhibited the ERK and AKT signaling. In conclusion, the low expression of GIGYF1 gene can inhibit the occu …
GRB10 interacting GYF protein 1 (GIGYF1) binds to the N-terminal region of Grb10, regulates multiple signaling pathways. ...Meanwhile …
GIGYF1/2 proteins use auxiliary sequences to selectively bind to 4EHP and repress target mRNA expression.
Peter D, Weber R, Sandmeir F, Wohlbold L, Helms S, Bawankar P, Valkov E, Igreja C, Izaurralde E. Peter D, et al. Genes Dev. 2017 Jun 1;31(11):1147-1161. doi: 10.1101/gad.299420.117. Epub 2017 Jul 11. Genes Dev. 2017. PMID: 28698298 Free PMC article.
In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding regions of GIGYF1 and GIGYF2 in complex with 4EHP, which reveal the molecular basis for the selectivity of the GIGYF1/2 proteins for …
In contrast to eIF4G, GIGYF1/2 bind selectively to 4EHP but not eIF4E. Here, we present crystal structures of the 4EHP-binding region …
38 results