LHX3 encodes a protein of a large protein family, members of which carry the LIM domain, a unique cysteine-rich zinc-binding domain. The encoded protein is a transcription factor that is required for pituitary development and motor neuron specification. Two transcript variants encoding distinct isoforms have been identified for this gene.[3]
Clinical significance
Mutations in this gene have been associated with a syndrome of combined pituitary hormone deficiency and rigid cervical spine.[3]
↑Sloop KW, Meier BC, Bridwell JL, Parker GE, Schiller AM, Rhodes SJ (Jan 2000). "Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties". Mol Endocrinol. 13 (12): 2212–25. doi:10.1210/me.13.12.2212. PMID10598593.
↑Sloop KW, Showalter AD, Von Kap-Herr C, Pettenati MJ, Rhodes SJ (May 2000). "Analysis of the human LHX3 neuroendocrine transcription factor gene and mapping to the subtelomeric region of chromosome 9". Gene. 245 (2): 237–43. doi:10.1016/S0378-1119(00)00025-1. PMID10717474.
↑Jurata LW, Pfaff SL, Gill GN (February 1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". J. Biol. Chem. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID9452425.
Further reading
Zhadanov AB, Bertuzzi S, Taira M, et al. (1995). "Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets of neural and neuroendocrine tissues". Dev. Dyn. 202 (4): 354–64. doi:10.1002/aja.1002020405. PMID7626792.
Zhadanov AB, Copeland NG, Gilbert DJ, et al. (1995). "Genomic structure and chromosomal localization of the mouse LIM/homeobox gene Lhx3". Genomics. 27 (1): 27–32. doi:10.1006/geno.1995.1004. PMID7665181.
Jurata LW, Pfaff SL, Gill GN (1998). "The nuclear LIM domain interactor NLI mediates homo- and heterodimerization of LIM domain transcription factors". J. Biol. Chem. 273 (6): 3152–7. doi:10.1074/jbc.273.6.3152. PMID9452425.
Bach I, Rodriguez-Esteban C, Carrière C, et al. (1999). "RLIM inhibits functional activity of LIM homeodomain transcription factors via recruitment of the histone deacetylase complex". Nat. Genet. 22 (4): 394–9. doi:10.1038/11970. PMID10431247.
Glenn DJ, Maurer RA (2000). "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression". J. Biol. Chem. 274 (51): 36159–67. doi:10.1074/jbc.274.51.36159. PMID10593900.
Howard PW, Maurer RA (2000). "Identification of a conserved protein that interacts with specific LIM homeodomain transcription factors". J. Biol. Chem. 275 (18): 13336–42. doi:10.1074/jbc.275.18.13336. PMID10788441.
Parker GE, Sandoval RM, Feister HA, et al. (2000). "The homeodomain coordinates nuclear entry of the Lhx3 neuroendocrine transcription factor and association with the nuclear matrix". J. Biol. Chem. 275 (31): 23891–8. doi:10.1074/jbc.M000377200. PMID10818088.
Netchine I, Sobrier ML, Krude H, et al. (2000). "Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency". Nat. Genet. 25 (2): 182–6. doi:10.1038/76041. PMID10835633.
Schmitt S, Biason-Lauber A, Betts D, Schoenle EJ (2000). "Genomic structure, chromosomal localization, and expression pattern of the human LIM-homeobox3 (LHX 3) gene". Biochem. Biophys. Res. Commun. 274 (1): 49–56. doi:10.1006/bbrc.2000.3038. PMID10903894.
Sloop KW, Dwyer CJ, Rhodes SJ (2001). "An isoform-specific inhibitory domain regulates the LHX3 LIM homeodomain factor holoprotein and the production of a functional alternate translation form". J. Biol. Chem. 276 (39): 36311–9. doi:10.1074/jbc.M103888200. PMID11470784.
van Meyel DJ, Thomas JB, Agulnick AD (2003). "Ssdp proteins bind to LIM-interacting co-factors and regulate the activity of LIM-homeodomain protein complexes in vivo". Development. 130 (9): 1915–25. doi:10.1242/dev.00389. PMID12642495.
Kim SS, Kim Y, Shin YL, et al. (2004). "Clinical characteristics and molecular analysis of PIT1, PROP1,LHX3, and HESX1 in combined pituitary hormone deficiency patients with abnormal pituitary MR imaging". Horm. Res. 60 (6): 277–83. doi:10.1159/000074245. PMID14646405.
Dattani MT (2004). "Borjeson-Forssman-Lehmann syndrome: a novel pituitary phenotype due to mutation in a novel gene". J. Pediatr. Endocrinol. Metab. 16 (9): 1207–9. doi:10.1515/jpem.2003.16.9.1207. PMID14714741.
West BE, Parker GE, Savage JJ, et al. (2004). "Regulation of the follicle-stimulating hormone beta gene by the LHX3 LIM-homeodomain transcription factor". Endocrinology. 145 (11): 4866–79. doi:10.1210/en.2004-0598. PMID15271874.
Parker GE, West BE, Witzmann FA, Rhodes SJ (2005). "Serine/threonine/tyrosine phosphorylation of the LHX3 LIM-homeodomain transcription factor". J. Cell. Biochem. 94 (1): 67–80. doi:10.1002/jcb.20287. PMID15517599.
Sobrier ML, Attié-Bitach T, Netchine I, et al. (2006). "Pathophysiology of syndromic combined pituitary hormone deficiency due to a LHX3 defect in light of LHX3 and LHX4 expression during early human development". Gene Expr. Patterns. 5 (2): 279–84. doi:10.1016/j.modgep.2004.07.003. PMID15567726.