Disease relevance of Aes

• For animals treated with the AES reagents, toxicity varied with the pretargeting time interval and the administered activity [1].

High impact information on Aes

• The pattern of Grg5 expression in the mouse ventral forebrain and developing optic vesicles overlapped that previously reported for Six3 and Six6 [2].
• We examined whether the Q domain is used for dimerization between Grg proteins, using the yeast two-hybrid system and binding assays with glutathione S-transferase fusion proteins [3].
• However, at least two Grg proteins contain only the amino-terminal Q (glutamine-rich) domain [3].
• Deficiency of a related gene, amino terminal enhancer of split (Aes), causes pituitary anomalies and growth insufficiency [4].
• We therefore conclude that Grg5 enhances Runx2 activity in vivo [5].

Biological context of Aes

• We found that Grg proteins are able to dimerize through the Q domain and that dimerization requires a core of 50 amino acids [3].
• The 3' region of the Grg gene contains two functional polyadenylation sites that give rise to two transcripts that are differentially expressed among adult mouse tissues [6].
• This decreased trabecular bone formation is likely caused by a reduced recruitment of osteoblasts into the growth plate region of Grg5 null mice [7].
• Our data suggest that the coordinated transcriptional control of these genes occurs during development and that precise Hes and Grg pairings may play a role in mediating the morphogenesis of CNS and epithelialized structures [8].
• The 'long' Groucho family members containing five domains are repressors of Tcf-mediated transactivation, whereas Grg-5, which only contains the first two domains, acts as a de-repressor [9].

Anatomical context of Aes

• We also show that Runx2 haploinsufficiency in the absence of Grg5 results in a more severe delay in ossification of cranial sutures and fontanels than occurs with Runx2 haploinsufficiency on a wild-type background [5].
• To address this, we determined the expression of all Tcf and Grg/TLE family members in a panel of cell lines [9].
• Since nitric oxide (NO) is one of the major inflammatory parameters, we studied the effect of aqueous extracts of Spirodela polyrhixa (AESP) on NO production in lipopolysaccharide (LPS)-stimulated mouse peritoneal macrophages [10].
• AESP inhibited the secretion of NO in macrophages, without affecting cell viability [10].

Physical interactions of Aes

• Groucho homologue Grg5 interacts with the transcription factor Runx2-Cbfa1 and modulates its activity during postnatal growth in mice [5].

Other interactions of Aes

• We have isolated cDNAs representing multiple members of murine groucho homologues, designated Grg for groucho-related genes [11].
• The yeast two-hybrid system was used to identify a groucho homologue, Grg5, as a Runx2-interacting protein [5].
• Growth defect in Grg5 null mice is associated with reduced Ihh signaling in growth plates [7].
• A comparison of Notch, Hes and Grg expression during murine embryonic and post-natal development [8].
• However, the mouse Grg protein does not contain the region homologous to G-protein beta-subunits [12].

Analytical, diagnostic and therapeutic context of Aes

• TLE3 and AES have been shown to interact with TCF/LEF (transcripiton factors of the T cell-specific and lymphoid enhancer specific group) family members in cell culture systems [4].
• Coexpression of Grg5 with Grg1 reduces tumor burden [13].
• A null mutation of the Grg gene was constructed by gene targeting [14].
• An analysis by in situ hybridization of the spatial and temporal localization of Grg RNA expression revealed that, while the initial pattern of Grg expression was quite restricted, by midgestation Grg RNA was ubiquitously expressed in the developing embryo [12].
• CONCLUSION: This study indicates that 188Re can be used for radiolabeling of hapten in two-step radioimmunotherapy protocols with the AES technique [15].

References