Disease relevance of LBX1

• The mouse Lbx1 gene is located on chromosome 19 (region D) and the human LBX1 gene maps to the related q24 region of chromosome 10, known as a breakpoint region in translocations t(7;10) and t(10;14) involved in T-cell leukemias [1].
• We have previously shown that transduction of HOXD3, one of homeobox genes, into human lung cancer A549 cells enhances cell motility, invasion and metastasis [2].
• The mouse mutation Small eye (Sey), which has been proposed as a model for aniridia, results from defects in Pax-6, a gene containing paired-box and homeobox motifs that is specifically expressed in the developing eye and brain [3].
• The cardiac homeobox protein Nkx2-5 is essential in cardiac development, and mutations in Csx (which encodes Nkx2-5) cause various congenital heart diseases [4].
• Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse [5].

Psychiatry related information on LBX1

• CONCLUSION: Decreased thalamic expression of DLX1 in schizophrenia and bipolar disorder with psychosis suggests shared genetic deficits in expression of this homeobox gene [6].
• The DiGeorge syndrome minimal critical region contains a goosecoid-like (GSCL) homeobox gene that is expressed early in human development [7].
• In this review we focus on a number of transcription factor families (homeobox, STAT, and Ets), and on inhibitors of transcription factors (Id), which have been implicated in controlling the cell cycle not only in normal mammary gland development but also in breast tumorigenesis [8].
• Interference with homeobox gene expression as an avenue to the perturbation of early developmental processes and the production of hindbrain and craniofacial abnormalities is then proposed as a common basis for the translation and expression of several genetic mental retardation syndromes [9].

High impact information on LBX1

• Finally, retinoic acid receptors regulate many developmental control genes, including homeobox genes and growth factor genes [10].
• Homeobox transcription factors exert essential roles in embryogenesis and are thought to govern regenerative cell differentiation [11].
• In this issue of Cell, MacLean and colleagues (MacLean et al., 2005) describe a new homeobox gene cluster composed of genes selectively expressed in reproductive tissues [11].
• The mammalian homeobox transcription factor CDX2 has key roles in intestinal development and differentiation [12].
• Polyalanine expansion and frameshift mutations of the paired-like homeobox gene PHOX2B in congenital central hypoventilation syndrome [13].

Chemical compound and disease context of LBX1

• We previously reported that retinoic acid specifically induces human homeobox gene (HOX) expression in the embryonal carcinoma cell line NT2/D1 [14].
• These observations provide evidence that enhanced proliferation in N-ras-transformed cells compromises teratocarcinoma cell differentiation by a mechanism that transiently suppresses homeobox gene induction and implies a central role for homeobox genes in RA-induced cell differentiation [15].
• Several genes of potential biological and therapeutic interest were associated with each sarcoma type, including specific tyrosine kinases, transcription factors, and homeobox genes [16].
• A role for the homeobox protein Distal-less 3 in the activation of the glycoprotein hormone alpha subunit gene in choriocarcinoma cells [17].
• A novel human prostate-specific, androgen-regulated homeobox gene (NKX3.1) that maps to 8p21, a region frequently deleted in prostate cancer [18].

Biological context of LBX1

• PURPOSE: A previous study demonstrated that CTCF (CCCTC binding factor) regulates homeobox Pax6 gene expression in early embryonic stages and plays a dominant role in eye development [19].
• Altogether, our results strongly suggest the absolute requirement for cooperative events in association with homeobox gene up-regulation to induce T-cell leukemogenesis [20].
• Deletions of 2q14 that include the homeobox engrailed 1 (EN1) transcription factor are compatible with a normal phenotype [21].
• The identification of five new genes using a subclass-specific 5' primer, designed from the engrailed and Xanf1 sequences, suggests that there still remain several uncharacterized HB genes in the human genome [22].
• Within the serial array of vertebrate homeobox genes in the Hox complexes, it is possible to define a subgroup that is structurally homologous to the Drosophila homeotic gene Deformed (Dfd) [23].

Anatomical context of LBX1

• Based on a knocked-out mouse model and a few expression studies, TLX3 is regarded as a homeobox gene crucial for the development of the autonomic nervous system [24].
• In this paper, we report that functional inactivation of the homeobox gene Six2 results in premature and ectopic differentiation of mesenchymal cells into epithelia and depletion of the progenitor cell population within the metanephric mesenchyme [25].
• PURPOSE: Previous studies indicate that the CCCTC binding transcription factor (CTCF) regulates homeobox PAX6 gene transcription in corneal epithelial cells [26].
• Cone-rod dystrophy due to mutations in a novel photoreceptor-specific homeobox gene (CRX) essential for maintenance of the photoreceptor [27].
• Crx, an Otx-like homeobox gene, is expressed specifically in the photoreceptors of the retina and the pinealocytes of the pineal gland [28].

Associations of LBX1 with chemical compounds

• Involvement of Per-Arnt-Sim (PAS) kinase in the stimulation of preproinsulin and pancreatic duodenum homeobox 1 gene expression by glucose [29].
• However, in N-ras-transformed cell clones, RA-induced expression of these homeobox genes is delayed [15].
• The first thymidine, as well as the last three bases (TAA), were important for homeobox binding [30].
• This mutation is a G-->A transition altering an arginine residue to a histidine in a highly conserved location in the second helix of the homeobox of RIEG1 [31].
• A homeobox gene that is expressed specifically in adult human prostate, NKX3.1, the expression of which is regulated by androgen, maps to chromosome 8p21 [32].

Physical interactions of LBX1

• Here we show for the first time that SIRT2 interacts with the homeobox transcription factor, HOXA10, which was identified in a two-hybrid screen [33].
• Previously, we have demonstrated that GBX genes, a homeobox-containing human family of DNA-binding transcription factors consisting of GBX1 and GBX2, are overexpressed in a panel of human prostatic cancer cell lines (ie., TSU-pr1, PC3, DU145, and LNCaP) compared to normal prostate [34].
• Recently, inappropriate activation of the intestine-specific transcription factor like the homeobox gene complex CDX1 and CDX2 are found to be an important contributing factor in the induction of intestinal metaplasia in the stomach [35].
• The HOX11 gene encodes a DNA-binding nuclear transcription factor belonging to a distinct family of homeobox genes [36].
• Homeobox Msx1 interacts with p53 tumor suppressor and inhibits tumor growth by inducing apoptosis [37].

Enzymatic interactions of LBX1

• We show that HOXC13, but not a homeobox-deleted HOXC13, strongly activated the promoters of the genes, with the respective proximal promoter regions being sufficient for optimal activation [38].
• Our studies of human CFTR transcription focus on identifying transcription factors bound to an inverted CCAAT consensus or "Y-box element." The human homeodomain CCAAT displacement protein/cut homolog (CDP/cut) can bind to the Y-box element through a cut repeat and homeobox [39].

Regulatory relationships of LBX1

• This is the first report of a homeobox gene being specifically regulated by PBX2 and the second report of a vertebrate homeobox target gene of a PBX protein [40].
• CDX2 is known to regulate class I homeobox genes and its expression in hematopoietic cells may critically alter the balance between differentiation and proliferation [41].
• These results suggest that MLL fusion proteins impose a reversible block on myeloid differentiation through aberrant activation of a limited set of homeobox genes and Hox coregulators that are consistently expressed in MLL-associated leukemias [42].
• Multiple copies of the GLUT2TAAT motif were ligated 5' to a heterologous promoter and transfected into a PDX-1-expressing cell line (beta TC3) and into cell lines lacking the homeobox factor (InR1-G9 and JEG-3) [43].
• The present study examined the effects of SNH on homeobox genes in the colon cancer cell line HT 29 that expresses VIP receptors [44].

Other interactions of LBX1

• This duplicated region contained a disrupted extra copy of the DACTYLIN gene and the entire LBX1 and beta-TRCP genes, known to be involved in limb development [45].
• Thus, LBX1 and the protooncogene HOX11 map to a common chromosomal region, as do their Drosophila counterparts, the lady bird and 93Bal genes [1].
• Here, we report the cloning and sequencing of 31 homeobox (HB) sequences, identified using degenerate oligodeoxyribonucleotide primers, in a polymerase chain reaction with cDNA derived from a purified CD34+ population of human haemopoietic cells [22].
• Haploinsufficiency of the human homeobox gene ALX4 causes skull ossification defects [46].
• A novel homeobox gene PITX3 is mutated in families with autosomal-dominant cataracts and ASMD [47].

Analytical, diagnostic and therapeutic context of LBX1

• Homeobox (HOX) 11 and HOX11L2 expression was determined by real-time PCR [48].
• Immunohistochemistry on appendicular sections after E10.5 demonstrated that Pitx2 neatly marked the areas of muscle anlagen, that Pax3, Lbx1, and the muscle regulatory factors (MRFs) stained only subsets of Pitx2(+) cells within these areas, and that virtually all Pitx2(+) cells in these areas express at least one of these known myogenic markers [49].
• Gene targeting in mouse embryo-derived stem cells has been used to disrupt the homeobox gene hox-1 [50].
• Zmhox1a (Zea mays homeobox) is an unidentified maize gene mapping to the long arm of chromosome 8 [51].
• Sequence analysis and expression patterns divide the maize knotted1-like homeobox genes into two classes [52].

References