DLX5
Homeobox protein DLX-5 is a protein that in humans is encoded by the distal-less homeobox 5 gene, or DLX5 gene.[1][2]
Function
This gene encodes a member of a homeobox transcription factor gene family similar to the Drosophila distal-less (Dll) gene. The encoded protein may play a role in bone development and fracture healing. Current research holds that the homeobox gene family is important in appendage development. DLX5 and DLX6 can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. Mutation in this gene, which is located in a tail-to-tail configuration with another member of the family on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation.[2]
DLX5 also acts as the early BMP-responsive transcriptional activator needed for osteoblast differentiation by stimulating the up-regulation of a variety of promoters (ALPL promoter, SP7 promoter, MYC promoter).[3]
Clinical significance
Mutations in the DLX5 gene have been shown to be involved in the hand and foot malformation syndrome.[4] SHFM is a heterogenous limb defect in which the development of the central digital rays is hindered, leading to missing central digits and claw-like distal extremities. Other defects associated with DLX5 include sensorineural hearing loss, mental retardation, ectodermal and craniofacial findings, and orofacial clefting.
In mice, the targeted disruption of DLX1, DLX2, DLX1/2, or DLX5 orthologs yields craniofacial, bone, and vestibular defects. If DLX5 is disrupted in conjunction with DLX6, bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.[5]
Developmental Stage
DLX5 begins to express DLX5 protein in the facial and branchial arch mesenchyme, otic vesicles, and frontonasal ectoderm at around day 8.5-9. By day 12.5, DLX5 protein begins to be expressed in the brain, bones, and all remaining skeletal structures. Expression in the brain and skeleton begins to decrease by day 17.[3]
Interactions
DLX5 has been shown to interact with DLX1,[5] DLX2,[6] DLX6,[5] MSX1[6] and MSX2.[6]
References
- ↑ Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K et al. (Apr 1994). "Cloning and characterization of two members of the vertebrate Dlx gene family". Proc Natl Acad Sci U S A 91 (6): 2250–4. doi:10.1073/pnas.91.6.2250. PMC 43348. PMID 7907794.
- ↑ 2.0 2.1 "Entrez Gene: DLX5 distal-less homeobox 5".
- ↑ 3.0 3.1 "Homeobox protein DLX-5".
- ↑ Shamseldin HE, Faden MA, Alashram W, Alkuraya FS (November 2011). "Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation". J Med Genet 49 (1): 16–20. doi:10.1136/jmedgenet-2011-100556. PMID 22121204.
- ↑ 5.0 5.1 5.2 Robledo RF, Rajan L, Li X, Lufkin T (2002). "The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development". Genes Dev. 16 (9): 1089–101. doi:10.1101/gad.988402. PMC 186247. PMID 12000792.
- ↑ 6.0 6.1 6.2 Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C (May 1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism". Mol. Cell. Biol. 17 (5): 2920–32. PMC 232144. PMID 9111364.
Further reading
- Bapat S, Galande S (2005). "Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome.". BioEssays 27 (7): 676–80. doi:10.1002/bies.20266. PMID 15954098.
- Scherer SW, Poorkaj P, Massa H et al. (1995). "Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.". Hum. Mol. Genet. 3 (8): 1345–54. doi:10.1093/hmg/3.8.1345. PMID 7987313.
- Hillier LD, Lennon G, Becker M et al. (1997). "Generation and analysis of 280,000 human expressed sequence tags.". Genome Res. 6 (9): 807–28. doi:10.1101/gr.6.9.807. PMID 8889549.
- Zhang H, Hu G, Wang H et al. (1997). "Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism.". Mol. Cell. Biol. 17 (5): 2920–32. PMC 232144. PMID 9111364.
- Newberry EP, Latifi T, Towler DA (1999). "The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter.". Biochemistry 38 (33): 10678–90. doi:10.1021/bi990967j. PMID 10451362.
- Eisenstat DD, Liu JK, Mione M et al. (1999). "DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation.". J. Comp. Neurol. 414 (2): 217–37. doi:10.1002/(SICI)1096-9861(19991115)414:2<217::AID-CNE6>3.0.CO;2-I. PMID 10516593.
- Masuda Y, Sasaki A, Shibuya H et al. (2001). "Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function.". J. Biol. Chem. 276 (7): 5331–8. doi:10.1074/jbc.M008590200. PMID 11084035.
- Yu G, Zerucha T, Ekker M, Rubenstein JL (2002). "Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins.". Brain Res. Dev. Brain Res. 130 (2): 217–30. doi:10.1016/S0165-3806(01)00239-5. PMID 11675124.
- Sasaki A, Masuda Y, Iwai K et al. (2002). "A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1.". J. Biol. Chem. 277 (25): 22541–6. doi:10.1074/jbc.M109728200. PMID 11959851.
- Willis DM, Loewy AP, Charlton-Kachigian N et al. (2002). "Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex.". J. Biol. Chem. 277 (40): 37280–91. doi:10.1074/jbc.M206482200. PMID 12145306.
- Strausberg RL, Feingold EA, Grouse LH et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Scherer SW, Cheung J, MacDonald JR et al. (2003). "Human chromosome 7: DNA sequence and biology.". Science 300 (5620): 767–72. doi:10.1126/science.1083423. PMC 2882961. PMID 12690205.
- Okita C, Meguro M, Hoshiya H et al. (2004). "A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids.". Genomics 81 (6): 556–9. doi:10.1016/S0888-7543(03)00052-1. PMID 12782124.
- Hillier LW, Fulton RS, Fulton LA et al. (2003). "The DNA sequence of human chromosome 7.". Nature 424 (6945): 157–64. doi:10.1038/nature01782. PMID 12853948.
- Ota T, Suzuki Y, Nishikawa T et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Gerhard DS, Wagner L, Feingold EA et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Rual JF, Venkatesan K, Hao T et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network.". Nature 437 (7062): 1173–8. doi:10.1038/nature04209. PMID 16189514.
- Kimura K, Wakamatsu A, Suzuki Y et al. (2006). "Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.". Genome Res. 16 (1): 55–65. doi:10.1101/gr.4039406. PMC 1356129. PMID 16344560.
External links
- DLX5 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
| |||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||