FOXC2
FOXC2
포크헤드 관련 단백질 FKHL14(FKHL14), 전사인자 FKH-14, 또는 메센하임 포크헤드 단백질 1(MFH1)로도 알려진 포크헤드 박스 단백질 C2(FOXC2)는 FOXC2 [5][6]유전자에 의해 인체에서 암호화되는 단백질이다.FOXC2는 포크 헤드 박스(FOX) 계열의 전사 인자의 구성원입니다.
구조 및 기능
단백질의 길이는 501개의 아미노산입니다.그 유전자는 인트론을 가지고 있지 않다; 단일 엑손의 크기는 [6][7]약 1.5kb이다.
FOX 전사인자는 발달 중에 발현되며 많은 세포 및 발달 분화 과정과 관련이 있다.FOXC2는 팟구 분화와 사구체 기저막의 성숙을 포함한 신장의 초기 발달에 필요하다.그것은 또한 [8]심장의 초기 발달에 관여한다.
지방세포에서 FOXC2의 발현 증가는 갈색 지방조직의 양을 증가시켜 저중량 및 [9][10]인슐린에 대한 민감도를 높일 수 있다.
질병에서의 역할
FOXC2의 부재는 림프 밸브의 형성에 실패하여 림프 리모듈링에 문제가 있는 것으로 나타났다.FOXC2 유전자의 많은 돌연변이가 림프데마-디스티치아증 [11][12]증후군과 관련되었으며, 또한 FOXC2의 다형성과 하지정맥류 [12]사이에 연관성이 있을 수 있다는 것이 제시되었다.[13]
FOXC2는 암 전이에도 관여한다.특히 상피세포가 상피-간엽 전이(EMT)를 거쳐 간엽성 외관세포가 되었을 때 FOXC2의 발현을 유도한다.EMT는 달팽이, 트위스트, 구스코이드, TGF-베타 [14]1을 포함한 많은 유전자에 의해 유도될 수 있다.FOXC2의 과발현은 [8]전이성이 높은 유방암의 하위 유형에서 발견되었다.고도 전이성 유방암 모델에서 shRNA를 이용한 FOXC2 발현 억제는 이들의 전이 [15]능력을 차단한다.
레퍼런스
- ^ a b c GRCh38: 앙상블 릴리즈 89: ENSG00000176692 - 앙상블, 2017년 5월
- ^ a b c GRCm38: 앙상블 릴리즈 89: ENSMUSG000046714 - 앙상블, 2017년 5월
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Kaestner KH, Bleckmann SC, Monaghan AP, Schlöndorff J, Mincheva A, Lichter P, Schütz G (June 1996). "Clustered arrangement of winged helix genes fkh-6 and MFH-1: possible implications for mesoderm development". Development. 122 (6): 1751–8. doi:10.1242/dev.122.6.1751. PMID 8674414.
- ^ a b Miura N, Iida K, Kakinuma H, Yang XL, Sugiyama T (May 1997). "Isolation of the mouse (MFH-1) and human (FKHL 14) mesenchyme fork head-1 genes reveals conservation of their gene and protein structures". Genomics. 41 (3): 489–92. doi:10.1006/geno.1997.4695. PMID 9169153.
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- ^ Ng MY, Andrew T, Spector TD, Jeffery S (March 2005). "Linkage to the FOXC2 region of chromosome 16 for varicose veins in otherwise healthy, unselected sibling pairs". J. Med. Genet. 42 (3): 235–9. doi:10.1136/jmg.2004.024075. PMC 1736007. PMID 15744037.
- ^ Battula VL, Evans KW, Hollier BG, Shi Y, Marini FC, Ayyanan A, Wang RY, Brisken C, Guerra R, Andreeff M, Mani SA (June 2010). "Epithelial-Mesenchymal Transition-Derived Cells Exhibit Multi-Lineage Differentiation Potential Similar to Mesenchymal Stem Cells". Stem Cells. 28 (8): 1435–45. doi:10.1002/stem.467. PMC 3523728. PMID 20572012.
- ^ Mani SA, Yang J, Brooks M, Schwaninger G, Zhou A, Miura N, Kutok JL, Hartwell K, Richardson AL, Weinberg RA (June 2007). "Mesenchyme Forkhead 1 (FOXC2) plays a key role in metastasis and is associated with aggressive basal-like breast cancers". Proc. Natl. Acad. Sci. U.S.A. 104 (24): 10069–74. Bibcode:2007PNAS..10410069M. doi:10.1073/pnas.0703900104. PMC 1891217. PMID 17537911.
추가 정보
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- Witte MH, Erickson RP, Khalil M, et al. (2009). "Lymphedema-distichiasis syndrome without FOXC2 mutation: evidence for chromosome 16 duplication upstream of FOXC2". Lymphology. 42 (4): 152–60. PMID 20218083.
- de Mooij YM, van den Akker NM, Bekker MN, et al. (2009). "Abnormal Shh and FOXC2 expression correlates with aberrant lymphatic development in human fetuses with increased nuchal translucency". Prenat. Diagn. 29 (9): 840–6. doi:10.1002/pd.2316. PMID 19548265. S2CID 2293233.
- Sano H, Leboeuf JP, Novitskiy SV, et al. (2010). "The Foxc2 transcription factor regulates tumor angiogenesis". Biochem. Biophys. Res. Commun. 392 (2): 201–6. doi:10.1016/j.bbrc.2010.01.015. PMC 2822046. PMID 20060810.
- Vreeburg M, Heitink MV, Damstra RJ, et al. (2008). "Lymphedema-distichiasis syndrome: a distinct type of primary lymphedema caused by mutations in the FOXC2 gene". Int. J. Dermatol. 47 Suppl 1: 52–5. doi:10.1111/j.1365-4632.2008.03962.x. PMID 18986489. S2CID 10265549.
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