Disease relevance of R1b

• The rat homeobox gene, rHox, was cloned from a rat osteosarcoma cDNA library [1].
• We have examined the expression of POU homeobox genes in human breast cancer cell lines and human breast tissue samples [2].
• Abnormal expression of homeobox genes may lead to the development of leukemias, lymphomas, and solid tumors [2].
• Transforming growth factor beta induction of insulin gene expression is mediated by pancreatic and duodenal homeobox gene-1 in rat insulinoma cells [3].

High impact information on R1b

• We have identified the 30-zinc finger protein OAZ as a DNA-binding factor that associates with Smads in response to BMP2, forming a complex that transcriptionally activates the homeobox regulator of Xenopus mesoderm and neural development, Xvent-2 [4].
• The liver-specific transcription factor LF-B1 contains a highly diverged homeobox DNA binding domain [5].
• The predicted GHF-1 sequence contains a region, near its C-terminus, that exhibits considerable similarity to a homeobox consensus sequence [6].
• The homeobox transcription factor Gax is expressed in quiescent vascular smooth muscle cells (VSMCs), and its expression is downregulated by vascular injury or other conditions that lead to VSMC proliferation [7].
• These data suggest that cycle progression, integrin expression, and cell migration can be regulated in VSMCs by the homeobox gene product Gax [7].

Biological context of R1b

• Vertebrate Hox homeobox genes are transcription factors which regulate antero-posterior axial identity in embryogenesis, presumably through activation and/or repression of downstream target genes [8].
• Gene expression within the central nervous system is regulated by complex interactions of DNA-binding proteins, among which are the POU domain-containing proteins, which are distantly related to homeobox proteins [9].
• The results of these comparisons support the view that in mammals and most likely the vertebrates, four clusters of homeobox genes exist that were created by duplications of an entire primordial gene cluster [10].
• Accordingly, we screened adult and fetal human smooth muscle cell cDNA libraries with a degenerate oligonucleotide corresponding to a highly conserved region of the homeodomain with the idea that homeobox genes, if present, would display a smooth muscle cell phenotype-dependent pattern of expression [11].
• Antennapedia-class vertebrate homeobox genes have been classified with regard to their chromosomal locations and nucleotide sequence similarities within the 183-base-pair homeobox domain [10].

Anatomical context of R1b

• A typical example is the cerebellum with an almost exclusive expression of R1b in the Purkinje cells and of R1a in the granule, stellate, and basket cells [12].
• Immunocytochemical distribution of the GABA(B) receptor splice variants GABA(B) R1a and R1b in the rat CNS and dorsal root ganglia [13].
• Differences in expression of homeobox transcription factors in proximal and distal human small intestine [14].
• Restricted expression of homeobox genes distinguishes fetal from adult human smooth muscle cells [11].
• Northern blotting of adult and fetal tissues revealed low and restricted expression of all five homeobox genes [11].

Associations of R1b with chemical compounds

• The homeobox factor PDX-1 is a key regulator of pancreatic morphogenesis and glucose homeostasis; targeted disruption of the PDX-1 gene leads to pancreatic agenesis in pdx-1(-/-) homozygotes [15].
• A novel homeobox protein which recognizes a TGT core and functionally interferes with a retinoid-responsive motif [16].
• The expression of the PEM: homeobox gene from its androgen-dependent Sertoli-specific proximal promoter (Pp) was dramatically reduced more than 100-fold in response to irradiation [17].
• Here we describe a screening protocol for homeobox cDNAs that utilizes a short oligonucleotide probe with inosine residues incorporated at positions of maximum codon degeneracy [18].

Regulatory relationships of R1b

• Furthermore, PACAP and NGF differentially regulated the expression of mammalian achaete-scute homologue and paired homeobox 2b genes, transcription factors instrumental for sympathoadrenal development [19].

Other interactions of R1b

• The caudal-related homeobox transcription factor (Cdx2) plays an important role in intestinal development, differentiation, and homeostasis [20].
• Differential expression of the homeobox gene Pitx3 in midbrain dopaminergic neurons [21].
• The homeobox genes Lhx7 and Gbx1 are expressed in the basal forebrain cholinergic system [22].
• A highly active homeobox gene promoter regulated by Ets and Sp1 family members in normal granulosa cells and diverse tumor cell types [23].
• Three of these regions (positions -41 to -58, -113 to -124, and -149 to -156) correspond to previously identified binding sites for the pituitary-specific, homeobox protein, Pit-1/GHF-1 [24].

Analytical, diagnostic and therapeutic context of R1b

• To this aim, we have mapped the GABA(B)R1 (R1a) and GABA(B)R1b (R1b) transcript distribution in the rat brain using in situ hybridization [12].
• Northern blot analysis revealed the presence of both transcripts in the rat brain using specific cDNA probes for GABA(B)R1a and R1b, respectively [25].
• Sequence analyses indicate that the expansion of the primordial gene cluster complex was accompanied by diversification, whereas conservation predominated after the duplications of entire homeobox gene clusters [10].
• Electrophoretic mobility shift assay experiments using specific antisera identified the homeobox protein cdx-2/3 (which designates the same homeobox protein called cdx-2 for mice and cdx-3 for hamsters) as a major component of the G1-Gc2 complex in islet and intestinal cells [26].
• Molecular cloning and evolutional analysis of a mammalian homologue of the Distal-less 3 (Dlx-3) homeobox gene [27].

References