| 词条 | MSX1 |
| 释义 |
FunctionThis gene encodes a member of the muscle segment homeobox gene family. The encoded protein functions as a transcriptional repressor during embryogenesis through interactions with components of the core transcription complex and other homeoproteins. It may also have roles in limb-pattern formation, craniofacial development, in particular, odontogenesis, and tumor growth inhibition. There is also strong evidence from sequencing studies of candidate genes involved in clefting that mutations in the MSX1 gene may be associated in the pathogenesis of cleft lip and palate.[5][6][7][8] Mutations in this gene, which was once known as homeobox 7, have also been associated with Witkop syndrome, Wolf-Hirschhorn syndrome, and autosomal dominant hypodontia.[9] Haploinsufficiency of MSX1 protein affects the development of all teeth, preferentially third molars and second premolars. The effect of haploinsufficiency of PAX9 on the development of incisors and premolars is probably caused by a deficiency of MSX1 protein.[10] Phenotypes caused by deficiency of MSX1 protein might depend on the localization of mutations and their effect on the protein structure and function. Two substitution mutations, Arg196Pro and Met61Lys cause only familial non-syndromic tooth agenesis. Frameshift mutations, Ser202Stop mutation, resulting in a protein that lacks the C-terminal end of the homeodomain, impairs not only teeth but also nail formation, while Ser105Stop mutation, causing complete absence of the MSX1 homeodomain, is responsible for the most severe phenotype, which includes orofacial clefts with accompanied tooth agenesis.[10] MSX1 is one of the strongest candidate genes for specific forms of tooth agenesis, mutations in this gene was detected only in some affected individuals. Genes expressed in the early dental epithelium in mice such as Bmp4, Bmp7, Dlx2, Dlx5, Fgf1, Fgf2, Fgf4, Fgf8, Lef1, Gli2, and Gli3 are also potential candidates. Based on existing evidence, it seems possible that both hypodontia and oligodontia are heterogeneous traits, caused by several independent defective genes, which act along or in combination with other genes and lead to specific phenotypes.[10] MSX1 is found to have a linkage with Witkop syndrome, also known as “tooth and nail syndrome” or “nail dysgenesis and hypodontia” since mutations in MSX1 were shown to be associated with tooth agenesis. There is a linkage found between TNS and markers surrounding the MSX1 locus and it showed that a nonsense mutation (S202X) in MSX1 cosegregated with the TNS phenotype in a three-generation family.[11] InteractionsMSX1 has been shown to interact with DLX5,[12] CREB binding protein,[4] Sp1 transcription factor,[4] DLX2,[12] TATA binding protein[4][12][13] and Msh homeobox 2.[12] LHX2, a LIMtype homeoprotein, is a protein partner for MSX1 in vitro and in cellular extracts. The interaction between MSX1 and LHX2 is mediated through the homeodomain-containing regions of both proteins. MSX1 and LHX2 form a protein complex in the absence of DNA, and that DNA binding by either protein alone can occur at the expense of protein complex formation.[14] References1. ^{{cite journal | vauthors = Hewitt JE, Clark LN, Ivens A, Williamson R | title = Structure and sequence of the human homeobox gene HOX7 | journal = Genomics | volume = 11 | issue = 3 | pages = 670–8 | date = Nov 1991 | pmid = 1685479 | doi = 10.1016/0888-7543(91)90074-O }} 2. ^{{cite journal | vauthors = McAlpine PJ, Shows TB | title = Nomenclature for human homeobox genes | journal = Genomics | volume = 7 | issue = 3 | pages = 460 | date = Jul 1990 | pmid = 1973146 | doi = 10.1016/0888-7543(90)90186-X }} 3. ^{{cite journal | vauthors = Sarapura VD, Strouth HL, Gordon DF, Wood WM, Ridgway EC | title = Msx1 is present in thyrotropic cells and binds to a consensus site on the glycoprotein hormone alpha-subunit promoter | journal = Molecular Endocrinology | volume = 11 | issue = 12 | pages = 1782–94 | date = Nov 1997 | pmid = 9369446 | doi = 10.1210/me.11.12.1782 }} 4. ^1 2 3 {{cite journal | vauthors = Shetty S, Takahashi T, Matsui H, Ayengar R, Raghow R | title = Transcriptional autorepression of Msx1 gene is mediated by interactions of Msx1 protein with a multi-protein transcriptional complex containing TATA-binding protein, Sp1 and cAMP-response-element-binding protein-binding protein (CBP/p300) | journal = The Biochemical Journal | volume = 339 | issue = 3 | pages = 751–8 | date = May 1999 | pmid = 10215616 | pmc = 1220213 | doi = 10.1042/0264-6021:3390751 }} 5. ^{{cite journal | vauthors = Dixon MJ, Marazita ML, Beaty TH, Murray JC | title = Cleft lip and palate: understanding genetic and environmental influences | journal = Nature Reviews. Genetics | volume = 12 | issue = 3 | pages = 167–78 | date = Mar 2011 | pmid = 21331089 | pmc = 3086810 | doi = 10.1038/nrg2933 }} 6. ^{{cite journal | vauthors = van den Boogaard MJ, Dorland M, Beemer FA, van Amstel HK | title = MSX1 mutation is associated with orofacial clefting and tooth agenesis in humans | journal = Nature Genetics | volume = 24 | issue = 4 | pages = 342–3 | date = Apr 2000 | pmid = 10742093 | doi = 10.1038/74155 }} 7. ^{{cite journal | vauthors = Jezewski PA, Vieira AR, Nishimura C, Ludwig B, Johnson M, O'Brien SE, Daack-Hirsch S, Schultz RE, Weber A, Nepomucena B, Romitti PA, Christensen K, Orioli IM, Castilla EE, Machida J, Natsume N, Murray JC | title = Complete sequencing shows a role for MSX1 in non-syndromic cleft lip and palate | journal = Journal of Medical Genetics | volume = 40 | issue = 6 | pages = 399–407 | date = Jun 2003 | pmid = 12807959 | pmc = 1735501 | doi = 10.1136/jmg.40.6.399 }} 8. ^{{cite journal | vauthors = Suzuki Y, Jezewski PA, Machida J, Watanabe Y, Shi M, Cooper ME, Viet le T, Nguyen TD, Hai H, Natsume N, Shimozato K, Marazita ML, Murray JC | title = In a Vietnamese population, MSX1 variants contribute to cleft lip and palate | journal = Genetics in Medicine | volume = 6 | issue = 3 | pages = 117–25 | year = 2004 | pmid = 15354328 | doi = 10.1097/01.GIM.0000127275.52925.05 | url = http://meta.wkhealth.com/pt/pt-core/template-journal/lwwgateway/media/landingpage.htm?issn=1098-3600&volume=6&issue=3&spage=117 }} 9. ^{{cite web | title = Entrez Gene: MSX1 msh homeobox 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4487| accessdate = }} 10. ^1 2 {{cite journal | vauthors = Mostowska A, Kobielak A, Trzeciak WH | title = Molecular basis of non-syndromic tooth agenesis: mutations of MSX1 and PAX9 reflect their role in patterning human dentition | journal = European Journal of Oral Sciences | volume = 111 | issue = 5 | pages = 365–70 | date = Oct 2003 | pmid = 12974677 | doi = 10.1034/j.1600-0722.2003.00069.x }} 11. ^{{cite journal | vauthors = Jumlongras D, Bei M, Stimson JM, Wang WF, DePalma SR, Seidman CE, Felbor U, Maas R, Seidman JG, Olsen BR | title = A nonsense mutation in MSX1 causes Witkop syndrome | journal = American Journal of Human Genetics | volume = 69 | issue = 1 | pages = 67–74 | date = Jul 2001 | pmid = 11369996 | pmc = 1226049 | doi = 10.1086/321271 }} 12. ^1 2 3 {{cite journal | vauthors = Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C | title = Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2920–32 | date = May 1997 | pmid = 9111364 | pmc = 232144 | doi=10.1128/mcb.17.5.2920}} 13. ^{{cite journal | vauthors = Zhang H, Catron KM, Abate-Shen C | title = A role for the Msx-1 homeodomain in transcriptional regulation: residues in the N-terminal arm mediate TATA binding protein interaction and transcriptional repression | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 93 | issue = 5 | pages = 1764–9 | date = Mar 1996 | pmid = 8700832 | pmc = 39855 | doi = 10.1073/pnas.93.5.1764 }} 14. ^{{cite journal | vauthors = Bendall AJ, Rincón-Limas DE, Botas J, Abate-Shen C | title = Protein complex formation between Msx1 and Lhx2 homeoproteins is incompatible with DNA binding activity | journal = Differentiation; Research in Biological Diversity | volume = 63 | issue = 3 | pages = 151–7 | date = Jul 1998 | pmid = 9697309 | doi = 10.1046/j.1432-0436.1998.6330151.x }} Further reading{{Refbegin|33em}}
External links
1 : Transcription factors |
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