Disease relevance of TLE4

• Transducin-like enhancer of split four/ Groucho (TLE-4) was over-expressed in adenomas compared to the ACTH carcinoma [1].
• We compared the effect of human endothelial cell culture supernatant (HECS), ESG (Ewing sarcoma growth factor), IL-6 (interleukin-6) and peritoneal macrophages on the recovery of hybridoma cells after fusion with respect to growth, stability and distribution of isotype variants [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].

High impact information on TLE4

• Furthermore, the Grg4 interaction and suppression of phosphorylation depends on Pax2 binding to its target DNA sequence and is independent of histone deacetylation [4].
• In this report, we demonstrate that the Groucho/TLE family protein, Grg4, interacts with Pax2 to suppress transactivation [4].
• The CCN2 promoter possesses an ET-1 response element, which maps to the previously identified basal control element-1 (BCE-1) site [5].
• Interestingly, Grg4 levels decrease following B-cell activation, suggesting temporal regulation of Grg4 [6].
• In addition, TLE1 and TLE4 are adjacent to the CDR [7].

Biological context of TLE4

• The QD transcript contains the first four TLE4 exons and an intronic sequence 3' of exon 4, demonstrating that QD is a splice variant of TLE4 [8].
• In contrast, later stages correlate with up-regulation of TLE2 and TLE4, and decreased expression of TLE1 [9].
• Mouse AES-1 and AES-2 proteins, probably resulting from alternative splicing, contain 202 and 196 amino acids, respectively, while mouse ESG protein consists of 771 amino acids [10].
• Molecular cloning and expression of mouse and human cDNA encoding AES and ESG proteins with strong similarity to Drosophila enhancer of split groucho protein [10].
• The N-terminal amino acid sequence suggests that BCE1 belongs to family 45 glycoside hydrolase (family 45 endoglucanase) [11].

Anatomical context of TLE4

• Thus, QD could act as a negative regulator of TLE4 function, in early B-cell differentiation [8].
• 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 [9].
• In addition, Grg2, Grg4 and Grg5 are expressed in the notochord [12].
• In conclusion, TC-ESG is a simple, non-invasive and non-radiologic technique that can substitute intra-sigmoid ESG and potentially can be used in the diagnosis of various pathologic conditions of sigmoid colon [13].

Other interactions of TLE4

• TLE1 is up-regulated and TLE2 and TLE4 are down-regulated to different extents during early stages of differentiation [9].
• Most detailed data exist for medaka, where 3 Tle genes have been described, Tle1, Tle3, and Tle4 [14].

Analytical, diagnostic and therapeutic context of TLE4

• The molecular mass of BCE1 was found to be 40 kDa by sodium dodecylsulfate polyacrylamide gel electrophoresis (SDS-PAGE) [11].

References