Disease relevance of TLE1

• We also found that within a human lung tumor tissue array, a significant number of carcinomas overexpress Grg1/TLE1 [1].
• Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in adenomas compared to the ACTH carcinoma [2].
• These included 72 controls (C), 659 early and suspect open angle glaucoma (ESG) with perimetric mean defect (MD) lower than 6 dB, and 242 confirmed moderate and advanced glaucomas (AG) with perimetric MD >/=6 dB [3].
• In the first were enzymes such as TEM-1 and TEM-2 including TLE-1, SHV-1, SHV-2, penicillinases of Klebsiella pneumoniae and CTX-1 [4].

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

• Human AES, TLE 1 and TLE 3 genes were mapped to chromosomes 19, 9 and 15, respectively, using human and Chinese hamster hybrid cell lines [9].
• TLE1 inhibits AML1-dependent transactivation of the T cell receptor (TCR) enhancers alpha and beta, which contain functional AML binding sites, in transfected Jurkat T cells [10].
• These results implicate phosphorylation in the activity of Groucho/TLE1 proteins and suggest that phosphorylated forms of higher molecular mass are involved in nuclear functions [11].
• We discuss these results in terms of the roles of PRH and TLE in cell differentiation and development [12].
• In addition, we show that the WD repeat domains of UNC-37 and of the human homolog, TLE1, are functionally interchangeable in VA motor neurons which suggests that this highly conserved protein domain may also specify motor neuron identity and synaptic choice in more complex nervous systems [13].

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

• We show that PRH and TLE proteins are co-expressed in hematopoietic cells and interact in co-immunoprecipitation assays [12].
• Affinity chromatography and far Western blotting studies show further that native Groucho/TLE proteins interact specifically with histone H3 and not with other core histones [27].

References