Disease relevance of Tle1

• Our data suggest that Grg1 overexpression contributes to malignancy in human lung cancers [1].

High impact information on Tle1

• 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 [2].
• In the DC compartment, the mutant protein Runx3(VWRPY-) promoted normally developed skin Langerhans cells but failed to restrain DC spontaneous maturation, indicating that this latter process involves Runx3-mediated repression through recruitment of Groucho/TLE [2].
• Rescue requires the transcription activation domain of AML1 but does not require the C-terminal VWRPY motif, which is conserved in all AML1 family members and has been shown to interact with the transcriptional corepressor, Groucho/transducin-like Enhancer of split [3].
• Grg1 acts as a lung-specific oncogene in a transgenic mouse model [1].
• Recruitment of the groucho-related protein TLE4 may be involved in converting Pax2 into a transcriptional repressor of Wt1 [4].

Biological context of Tle1

• TCF and Groucho-related genes influence pituitary growth and development [5].
• Transcripts of Grg4, a murine groucho-related gene, are detected in adjacent tissues to other murine neurogenic gene homologues during embryonic development [6].
• The murine grg (Groucho-related gene) products are believed to interact with transcription factors and repress transcription, thereby regulating cell proliferation and differentiation [7].
• Taken together, these results strongly suggest non-redundant roles for individual TLE proteins during both cell-determination and cell-differentiation events [8].

Anatomical context of Tle1

• Individual TLE proteins are also expressed in combinatorial as well as complementary patterns during the development of the cerebral cortex and spinal cord of mouse embryos [8].

Other interactions of Tle1

• We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes [9].
• Grg3, a murine Groucho-related gene, is expressed in the developing nervous system and in mesenchyme-induced epithelial structures [9].
• Although the C-terminal VWRPY motif-deficient mutant of Runx1, which cannot interact with the transcriptional corepressor Transducin-like enhancer of split (TLE), promoted the double-negative to double-positive transition, it did not efficiently repress CD4 expression [10].

Analytical, diagnostic and therapeutic context of Tle1

• Coexpression of Grg5 with Grg1 reduces tumor burden [1].
• Using PCR, we identified a specific DNA motif that is bound by Six3 and we demonstrated that Six3 acts as a potent transcriptional repressor upon its interaction with Groucho-related members [11].

References