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TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-β signaling.

Guca E, Suñol D, Ruiz L, Konkol A, Cordero J, Torner C, Aragon E, Martin-Malpartida P, Riera A, Macias MJ
Nucleic Acids Res 46 9220-9235 (2018)
Cited: 20 times
EuropePMC logo PMID: 30060237

Abstract

TGIF1 is a multifunctional protein that represses TGF-β-activated transcription by interacting with Smad2-Smad4 complexes. We found that the complex structure of TGIF1-HD bound to the TGACA motif revealed a combined binding mode that involves the HD core and the major groove, on the one hand, and the amino-terminal (N-term) arm and the minor groove of the DNA, on the other. We also show that TGIF1-HD interacts with the MH1 domain of Smad proteins, thereby indicating that TGIF1-HD is also a protein-binding domain. Moreover, the formation of the HD-MH1 complex partially hinders the DNA-binding site of the complex, preventing the efficient interaction of TGIF1-HD with DNA. We propose that the binding of the TGIF1 C-term to the Smad2-MH2 domain brings both the HD and MH1 domain into close proximity. This local proximity facilitates the interaction of these DNA-binding domains, thus strengthening the formation of the protein complex versus DNA binding. Once the protein complex has been formed, the TGIF1-Smad system would be released from promoters/enhancers, thereby illustrating one of the mechanisms used by TGIF1 to exert its function as an active repressor of Smad-induced TGF-β signaling.

Articles - 6fqp mentioned but not cited (1)

  1. TGIF1 homeodomain interacts with Smad MH1 domain and represses TGF-β signaling. Guca E, Suñol D, Ruiz L, Konkol A, Cordero J, Torner C, Aragon E, Martin-Malpartida P, Riera A, Macias MJ. Nucleic Acids Res 46 9220-9235 (2018)


Reviews citing this publication (2)

  1. Quo Vadis Biomolecular NMR Spectroscopy? Selenko P. Int J Mol Sci 20 E1278 (2019)
  2. Posttranslational Modifications in Conserved Transcription Factors: A Survey of the TALE-Homeodomain Superclass in Human and Mouse. Reichlmeir M, Elias L, Schulte D. Front Cell Dev Biol 9 648765 (2021)

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  2. Upregulation of miR-101a Suppresses Chronic Renal Fibrosis by Regulating KDM3A via Blockade of the YAP-TGF-β-Smad Signaling Pathway. Ding H, Xu Y, Jiang N. Mol Ther Nucleic Acids 19 1276-1289 (2020)
  3. Integrative ATAC-seq and RNA-seq Analysis of the Longissimus Muscle of Luchuan and Duroc Pigs. Miao W, Ma Z, Tang Z, Yu L, Liu S, Huang T, Wang P, Wu T, Song Z, Zhang H, Li Y, Zhou L. Front Nutr 8 742672 (2021)
  4. Mitochondrial transcription factor A in RORγt+ lymphocytes regulate small intestine homeostasis and metabolism. Fu Z, Dean JW, Xiong L, Dougherty MW, Oliff KN, Chen ZE, Jobin C, Garrett TJ, Zhou L. Nat Commun 12 4462 (2021)
  5. TGIF transcription factors repress acetyl CoA metabolic gene expression and promote intestinal tumor growth. Shah A, Melhuish TA, Fox TE, Frierson HF, Wotton D. Genes Dev 33 388-402 (2019)
  6. Magnoflorine Ameliorates Inflammation and Fibrosis in Rats With Diabetic Nephropathy by Mediating the Stability of Lysine-Specific Demethylase 3A. Chang L, Wang Q, Ju J, Li Y, Cai Q, Hao L, Zhou Y. Front Physiol 11 580406 (2020)
  7. Loss of IRF7 accelerates acute myeloid leukemia progression and induces VCAM1-VLA-4 mediated intracerebral invasion. Wang H, Zhang D, Cui X, Dai Y, Wang C, Feng W, Lv X, Li Y, Wang L, Ru Y, Zhang Y, Ren Q, Zheng G. Oncogene 41 2303-2314 (2022)
  8. Unveiling the dimer/monomer propensities of Smad MH1-DNA complexes. Ruiz L, Kaczmarska Z, Gomes T, Aragon E, Torner C, Freier R, Baginski B, Martin-Malpartida P, de Martin Garrido N, Marquez JA, Cordeiro TN, Pluta R, Macias MJ. Comput Struct Biotechnol J 19 632-646 (2021)
  9. Structural Insight into the Binding of TGIF1 to SIN3A PAH2 Domain through a C-Terminal Amphipathic Helix. He X, Nie Y, Zhou H, Hu R, Li Y, He T, Zhu J, Yang Y, Liu M. Int J Mol Sci 22 12631 (2021)
  10. Structures of the germline-specific Deadhead and thioredoxin T proteins from Drosophila melanogaster reveal unique features among thioredoxins. Freier R, Aragón E, Bagiński B, Pluta R, Martin-Malpartida P, Ruiz L, Condeminas M, Gonzalez C, Macias MJ. IUCrJ 8 281-294 (2021)
  11. An integrated co-expression network analysis reveals novel genetic biomarkers for immune cell infiltration in chronic kidney disease. Xia J, Hou Y, Cai A, Xu Y, Yang W, Huang M, Mou S. Front Immunol 14 1129524 (2023)
  12. Conformational landscape of multidomain SMAD proteins. Gomes T, Martin-Malpartida P, Ruiz L, Aragón E, Cordeiro TN, Macias MJ. Comput Struct Biotechnol J 19 5210-5224 (2021)
  13. Heparin-binding epidermal growth factor and fibroblast growth factor 2 rescue Müller glia-derived progenitor cell formation in microglia- and macrophage-ablated chick retinas. El-Hodiri HM, Bentley JR, Reske AG, Taylor OB, Palazzo I, Campbell WA, Halloy NR, Fischer AJ. Development 150 dev202070 (2023)
  14. Silencing of histone deacetylase 3 suppresses the development of esophageal squamous cell carcinoma through regulation of miR-494-mediated TGIF1. Yang Y, Zhang Y, Lin Z, Wu K, He Z, Zhu D, Zhao J, Zhang C, Fan Y. Cancer Cell Int 22 191 (2022)
  15. Single-nucleotide polymorphisms in FLT3, NLRP5, and TGIF1 are associated with litter size in Small-tailed Han sheep. Chen S, Tao L, He X, Di R, Wang X, Chu M. Arch Anim Breed 64 475-486 (2021)
  16. TGIF1 plays a carcinogenic role in esophageal squamous cell carcinoma through the Wnt/β‑catenin and Akt/mTOR signaling pathways. Kong L, Yu Y, Guan H, Jiang L, Sun F, Li X, Huang W, Li B. Int J Mol Med 47 77 (2021)
  17. Transcriptome and co-expression network analysis reveals the molecular mechanism of inosine monophosphate-specific deposition in chicken muscle. Yu B, Cai Z, Liu J, Zhao W, Fu X, Gu Y, Zhang J. Front Physiol 14 1199311 (2023)


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