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Gene Review

TLE1  -  transducin-like enhancer of split 1...

Homo sapiens

Synonyms: E(Sp1) homolog, ESG, ESG1, Enhancer of split groucho-like protein 1, GRG1, ...
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Disease relevance of TLE1


High impact information on TLE1

  • A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors [5].
  • Remarkably, this repression domain interacts specifically with hGrg, TLE1, and TLE2 proteins, all of which are members of the Groucho family of transcriptional corepressors [6].
  • We also find that the amino-terminal glutamine-rich domains of hGrg and TLE1 are sufficient to mediate dimerization of the two Groucho family proteins [6].
  • HES6 interacted with the corepressor transducin-like Enhancer of split 1 in yeast and mammalian cells through its WRPW COOH-terminal motif [7].
  • Thus, in CD8-lineage T cells, Runx3 regulates alphaE/CD103 in opposing regulatory modes and recruits Groucho/TLE to facilitate the transition from activation to repression [8].

Biological context of TLE1


Anatomical context of TLE1

  • In particular, TLE1 is robustly expressed in both neural progenitor cells and postmitotic neurons of the outer layers of the cortical plate, whereas TLE4 expression marks preferentially postmitotic neurons of the inner layers [14].
  • The yeast two-hybrid assay, gluthione S-transferase fusion protein pull-down assay and immuno-co-precipitation assay indicated that the Q domain of TLE1 is capable of binding gp130 intracellular domain, and the intracellular membrane proximal region of gp 130 containing conserved Box1 and Box2 motifs seemed essential for this interaction [15].
  • BF-1 is an essential regulator of neuronal differentiation during cerebral cortex development and represses transcription together with Gro/TLE1 [16].
  • Digital immunofluorescence microscopy results show that TLE1 and TLE2 are both associated with the nuclear matrix, and that a significant subset of each colocalizes with AML transcription factors [17].
  • These results provide the first direct evidence that TLE1 is an important negative regulator of postmitotic neuronal differentiation in the mammalian central nervous system [18].

Associations of TLE1 with chemical compounds

  • These results suggest that CK2 phosphorylation of serine 239 of Gro/TLE1 is important for its function during neuronal differentiation [19].
  • Mutation of serine 239 into alanine decreases Hes1-induced hyperphosphorylation of Gro/TLE1 and also reduces its nuclear association and transcription repression activity [19].
  • Phosphotungstic acid at low pH stained ICG and ASG strongly positive, and ESG weakly positive [20].
  • Pronase treatment in Epon sections for 24 h digested ASG alone, whereas in glycol-methacrylate embedded sections, ESG were digested first, ASG were digested thoroughly after 30 min, but ICG were not digested completely after 90 min [20].
  • METHODS: We used available data in the literature and information gathered from personal contacts with members of European Society of General Practice/Family Medicine (ESGP/FM) expert groups, European Academy of Teachers in General Practice (EURACT), and European General Practice Research Network (EGPRN) [21].

Enzymatic interactions of TLE1

  • Purification of Hes-1 identified the Groucho/transducin-like enhancer of split family of corepressors as the only significant Hes-1 interacting proteins in vivo [22].
  • The two full-length cDNAs encoding ESG1 (Enhancer of split groucho) and related AES (Amino Enhancer of split) proteins of 767 and 197 amino acids, respectively, were cloned and sequenced from the African frog Xenopus laevis [23].

Other interactions of TLE1

  • We also show that TLE1 and TLE2 are organized in a tandem array at chromosomal location 19p13.3, while TLE3 maps to 15q22 [24].
  • Finally, we show that a mutation in the PRH N-terminal domain that blocks the PRH-TLE1 interaction in vitro eliminates co-repression [12].
  • Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma [25].
  • The Q domain in AES shares high homology with those in the transcription co-repressor transducin-like enhancer of split (TLE) proteins [15].
  • Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif [26].

Analytical, diagnostic and therapeutic context of TLE1


  1. Grg1 acts as a lung-specific oncogene in a transgenic mouse model. Allen, T., van Tuyl, M., Iyengar, P., Jothy, S., Post, M., Tsao, M.S., Lobe, C.G. Cancer Res. (2006) [Pubmed]
  2. Patterns of gene expression in pituitary carcinomas and adenomas analyzed by high-density oligonucleotide arrays, reverse transcriptase-quantitative PCR, and protein expression. Ruebel, K.H., Leontovich, A.A., Jin, L., Stilling, G.A., Zhang, H., Qian, X., Nakamura, N., Scheithauer, B.W., Kovacs, K., Lloyd, R.V. Endocrine (2006) [Pubmed]
  3. Optic disc tomography and perimetry in controls, glaucoma suspects, and early and established glaucomas. DE LA Rosa, M.G., Gonzalez-Hernandez, M., Lozano-Lopez, V., Mendez, M.S., DE LA Vega, R.R. Optometry and vision science : official publication of the American Academy of Optometry (2007) [Pubmed]
  4. Immunological comparison of constitutive beta-lactamases of gram-negative bacteria by neutralization in zymogram gels: properties of anti-TEM-1 and anti-TEM-2 sera. Paul, G., Barthélémy, M., Philippon, A., Peduzzi, J., Gilly, L., Labia, R., Névot, P. Ann. Inst. Pasteur Microbiol. (1988) [Pubmed]
  5. A mitochondrial protein, Bit1, mediates apoptosis regulated by integrins and Groucho/TLE corepressors. Jan, Y., Matter, M., Pai, J.T., Chen, Y.L., Pilch, J., Komatsu, M., Ong, E., Fukuda, M., Ruoslahti, E. Cell (2004) [Pubmed]
  6. PRDI-BF1/Blimp-1 repression is mediated by corepressors of the Groucho family of proteins. Ren, B., Chee, K.J., Kim, T.H., Maniatis, T. Genes Dev. (1999) [Pubmed]
  7. HES6 acts as a transcriptional repressor in myoblasts and can induce the myogenic differentiation program. Gao, X., Chandra, T., Gratton, M.O., Quélo, I., Prud'homme, J., Stifani, S., St-Arnaud, R. J. Cell Biol. (2001) [Pubmed]
  8. Groucho/transducin-like Enhancer-of-split (TLE)-dependent and -independent transcriptional regulation by Runx3. Yarmus, M., Woolf, E., Bernstein, Y., Fainaru, O., Negreanu, V., Levanon, D., Groner, Y. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  9. Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein. Miyasaka, H., Choudhury, B.K., Hou, E.W., Li, S.S. Eur. J. Biochem. (1993) [Pubmed]
  10. Transcriptional repression by AML1 and LEF-1 is mediated by the TLE/Groucho corepressors. Levanon, D., Goldstein, R.E., Bernstein, Y., Tang, H., Goldenberg, D., Stifani, S., Paroush, Z., Groner, Y. Proc. Natl. Acad. Sci. U.S.A. (1998) [Pubmed]
  11. Affinity for the nuclear compartment and expression during cell differentiation implicate phosphorylated Groucho/TLE1 forms of higher molecular mass in nuclear functions. Husain, J., Lo, R., Grbavec, D., Stifani, S. Biochem. J. (1996) [Pubmed]
  12. The proline-rich homeodomain protein recruits members of the Groucho/Transducin-like enhancer of split protein family to co-repress transcription in hematopoietic cells. Swingler, T.E., Bess, K.L., Yao, J., Stifani, S., Jayaraman, P.S. J. Biol. Chem. (2004) [Pubmed]
  13. The Groucho-like transcription factor UNC-37 functions with the neural specificity gene unc-4 to govern motor neuron identity in C. elegans. Pflugrad, A., Meir, J.Y., Barnes, T.M., Miller, D.M. Development (1997) [Pubmed]
  14. Combinatorial expression patterns of individual TLE proteins during cell determination and differentiation suggest non-redundant functions for mammalian homologs of Drosophila Groucho. Yao, J., Liu, Y., Husain, J., Lo, R., Palaparti, A., Henderson, J., Stifani, S. Dev. Growth Differ. (1998) [Pubmed]
  15. The transcription co-repressor TLE1 interacted with the intracellular region of gpl30 through its Q domain. Liu, F., Liu, Y., Li, D., Zhu, Y., Ouyang, W., Xie, X., Jin, B. Mol. Cell. Biochem. (2002) [Pubmed]
  16. Antagonistic effects of Grg6 and Groucho/TLE on the transcription repression activity of brain factor 1/FoxG1 and cortical neuron differentiation. Marçal, N., Patel, H., Dong, Z., Belanger-Jasmin, S., Hoffman, B., Helgason, C.D., Dang, J., Stifani, S. Mol. Cell. Biol. (2005) [Pubmed]
  17. Groucho/TLE/R-esp proteins associate with the nuclear matrix and repress RUNX (CBF(alpha)/AML/PEBP2(alpha)) dependent activation of tissue-specific gene transcription. Javed, A., Guo, B., Hiebert, S., Choi, J.Y., Green, J., Zhao, S.C., Osborne, M.A., Stifani, S., Stein, J.L., Lian, J.B., van Wijnen, A.J., Stein, G.S. J. Cell. Sci. (2000) [Pubmed]
  18. Disrupted development of the cerebral hemispheres in transgenic mice expressing the mammalian Groucho homologue transducin-like-enhancer of split 1 in postmitotic neurons. Yao, J., Liu, Y., Lo, R., Tretjakoff, I., Peterson, A., Stifani, S. Mech. Dev. (2000) [Pubmed]
  19. Phosphorylation of serine 239 of Groucho/TLE1 by protein kinase CK2 is important for inhibition of neuronal differentiation. Nuthall, H.N., Joachim, K., Stifani, S. Mol. Cell. Biol. (2004) [Pubmed]
  20. Fine structure and cytochemistry of specific granules in the lamprey atrium. Shibata, Y., Yamamoto, T. Cell Tissue Res. (1976) [Pubmed]
  21. General practice east of Eden: an overview of general practice in Eastern Europe. Svab, I., Pavlic, D.R., Radić, S., Vainiomäki, P. Croat. Med. J. (2004) [Pubmed]
  22. Functional analysis of Hes-1 in preadipocytes. Ross, D.A., Hannenhalli, S., Tobias, J.W., Cooch, N., Shiekhattar, R., Kadesch, T. Mol. Endocrinol. (2006) [Pubmed]
  23. Cloning and developmental expression of Xenopus cDNAs encoding the Enhancer of split groucho and related proteins. Choudhury, B.K., Kim, J., Kung, H.F., Li, S.S. Gene (1997) [Pubmed]
  24. Epithelial expression and chromosomal location of human TLE genes: implications for notch signaling and neoplasia. Liu, Y., Dehni, G., Purcell, K.J., Sokolow, J., Carcangiu, M.L., Artavanis-Tsakonas, S., Stifani, S. Genomics (1996) [Pubmed]
  25. Identification of PNRC2 and TLE1 as activation function-1 cofactors of the orphan nuclear receptor ERRgamma. Hentschke, M., Borgmeyer, U. Biochem. Biophys. Res. Commun. (2003) [Pubmed]
  26. Molecular interaction between TLE1 and the carboxyl-terminal domain of HES-1 containing the WRPW motif. Grbavec, D., Stifani, S. Biochem. Biophys. Res. Commun. (1996) [Pubmed]
  27. The Groucho/transducin-like enhancer of split transcriptional repressors interact with the genetically defined amino-terminal silencing domain of histone H3. Palaparti, A., Baratz, A., Stifani, S. J. Biol. Chem. (1997) [Pubmed]
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