Disease relevance of Genes, erbA

• This is strongly supported by our observations that some naturally occurring TR beta mutants that have been associated with generalized thyroid hormone resistance as well as the v-erbA oncogene are defective in this activity [1].
• Thyroid hormone (T3) and the T3 receptor (TR) alpha gene are essential for bone development whereas adult hyperthyroidism increases the risk of osteoporotic fracture [2].
• Cloning and expression in Escherichia coli of the homoserine kinase (thrB) gene from Brevibacterium lactofermentum [3].

High impact information on Genes, erbA

• This new mechanism of action of v-ErbA together with its previously discovered dominant repressor effect on transcription of thyroid hormone-activated target genes may explain the contribution of the v-erbA oncogene to sarcomatogenic and leukemogenic transformation [4].
• v-erbA oncogene function in neoplasia correlates with its ability to repress retinoic acid receptor action [5].
• v-erbA oncogene activation entails the loss of hormone-dependent regulator activity of c-erbA [6].
• The v-erbA oncogene, one of the two oncogenes of the avian erythroblastosis virus, efficiently blocks erythroid differentiation and suppresses erythrocyte-specific gene transcription [6].
• Amino acid sequence comparisons revealed significant regional homology among the human estrogen receptor, the human glucocorticoid receptor, and the putative v-erbA oncogene product [7].

Biological context of Genes, erbA

• The c-erbA gene belongs to a multigene family that encodes transcriptional regulatory proteins including the v-erbA oncogene product, steroid hormone receptors, and the vitamin D3 receptor [8].
• In contrast, the v-erbA oncogene, a mutated, oncogenic version of TR alpha-1, partially but constitutively inhibited NGF-induced neuronal differentiation of PC12 cells and potentiated dexamethasone-induced chromaffin differentiation, giving rise to an aberrant "interlineage" cell phenotype [9].
• The v-erbA oncogene consists of an avian retroviral gag gene fused to a mutated thyroid hormone receptor [10].
• A genomic clone spanning the mouse rod transducin alpha subunit (Tr alpha) gene has been isolated by screening a mouse genomic library with a bovine Tr alpha cDNA clone [11].
• In AEV-transformed erythroleukemic cells the v-erbA gene product is likely to antagonize the function of triiodothyronine (T3) and retinoic acid (RA) receptors and thereby to block cell differentiation [12].

Anatomical context of Genes, erbA

• We investigated the effect of the v-erbA oncogene product, an altered thyroid hormone receptor, in chicken erythrocyte progenitor cells [13].
• Resistance to thyroid hormone (RTH) is caused by mutations of the thyroid hormone receptor beta (TR beta) gene [14].
• The v-erbA oncogene coding for a mutated form of the thyroid hormone (T3) receptor (TR alpha 1) increased the invasion capacity of the mouse B3.1 glial cell line [15].

Associations of Genes, erbA with chemical compounds

• It consists of 930 amino acids and contains a basic, cysteine-rich region (residues 568-645) with extensive homology to the glucocorticoid and estrogen receptors and the v-erbA oncogene protein [16].
• Thus, v-ski cooperates with tyrosine kinase oncogenes in a similar fashion to the v-erbA oncogene, however the pattern of genes affected by these two oncogenes is different [17].
• The v-erbA oncogene blocks expression of alpha2/beta1 integrin a normal inhibitor of erythroid progenitor proliferation [18].
• The well documented mitogenic and hormone regulatory effects of estrogen (E2) on pituitary cells are mediated via its nuclear receptor (ER), a cellular homolog of v-erbA oncogene [19].
• The v-erbA oncogene of avian erythroblastosis virus is derived from a cellular gene for a thyroid hormone (T4/T3 thyronine) receptor and encodes a DNA-binding protein found principally in the nucleus of the infected cell [20].

Gene context of Genes, erbA

• Chromosomal assignment of five cancer-associated rat genes: two thyroid hormone receptor (ERBA) genes, two ERBB genes and the retinoblastoma gene [21].
• To date, all individuals expressing the RTH phenotype have been found to harbor mutations in the thyroid hormone receptor beta (TR beta) gene that impair T3-mediated function [22].
• The first highly conserved ER region is not present in the truncated v-erbA gene, but shares some homology with the N-terminal end of the GR [23].
• These plasmids continued to express the second gene (thrB) of the operon as judged by their ability to complement a threonine auxotroph [24].
• In 1986, a connection between TR and cancer became evident when the chicken TRalpha1 was characterized as the c-erbA proto-oncogene, the cellular counterpart of the retroviral v-erbA oncogene [25].

References