Forkhead box protein

From Proteopedia
Jump to navigation Jump to search


Function

Forkhead box proteins (FOX) are transcription factors involved in regulation of gene expression.[1].

  • FOXO1 activation contributes to glucocorticoid-induced beta cell death[2].
  • FOXO3 negatively regulates autophagy in human cancer cells[3].
  • FOXP1 is a key reppressor of immune signaling in the CNS[4].
  • FOXP2 increases synaptic plasticity and dendrite connectivity[5]. See FOXP2 and Foxp2 bound specifically to DNA
  • FOXP3 drives T cell regulatory function[6]. See Forkhead Box Protein 3 and FOXP3 mutation- IPEX syndrome
  • FOXK1 is a tumor suppressor in facilitating angiogenesis and metastasis in breast cancer[7].
  • FOXM1 high expression is correlated with poor prognosis of patients with osteosarcoma[8]. See Forkhead box protein M1.
  • FOXN1 mutations result in phenotype of hairlessness and athymia resulting in severely compromised immune system.
  • FOXN3 is bispecific and recognizes two DNA motifs[9].

See also

Transcription and RNA Processing
Glucocorticoids
Steroid Hormones and their receptors.
Neurodevelopmental Disorders.

Disease

FOX mutations are implicated in congenital heart disease[10]. FOXC2 counteracts obesity, hypertriglyceridemia and diet-induced insulin resistance[11]. Truncated FOXC2 causes multiple lymphedema syndrome[12].

Structural highlights

FOX contain a DNA-binding motif (DBD) of 80-100 amino acids having a winged-helix shape.

  • .
  • . Water molecules shown as red spheres.
  • .

3D structures of FOX

FOX 3D structures


Human FoxO1 DNA-binding domain complex with DNA, Ca+2 and chloride ions, 3co6

Drag the structure with the mouse to rotate

ReferencesReferences

  1. ↑ Tuteja G, Kaestner KH. SnapShot: forkhead transcription factors I. Cell. 2007 Sep 21;130(6):1160. PMID:17889656 doi:http://dx.doi.org/10.1016/j.cell.2007.09.005
  2. ↑ Kaiser G, Gerst F, Michael D, Berchtold S, Friedrich B, Strutz-Seebohm N, Lang F, Haring HU, Ullrich S. Regulation of forkhead box O1 (FOXO1) by protein kinase B and glucocorticoids: different mechanisms of induction of beta cell death in vitro. Diabetologia. 2013 Jul;56(7):1587-95. doi: 10.1007/s00125-013-2863-7. Epub 2013, Feb 23. PMID:23435785 doi:http://dx.doi.org/10.1007/s00125-013-2863-7
  3. ↑ Zhu WL, Tong H, Teh JT, Wang M. Forkhead box protein O3 transcription factor negatively regulates autophagy in human cancer cells by inhibiting forkhead box protein O1 expression and cytosolic accumulation. PLoS One. 2014 Dec 29;9(12):e115087. doi: 10.1371/journal.pone.0115087., eCollection 2014. PMID:25546383 doi:http://dx.doi.org/10.1371/journal.pone.0115087
  4. ↑ Tang B, Becanovic K, Desplats PA, Spencer B, Hill AM, Connolly C, Masliah E, Leavitt BR, Thomas EA. Forkhead box protein p1 is a transcriptional repressor of immune signaling in the CNS: implications for transcriptional dysregulation in Huntington disease. Hum Mol Genet. 2012 Jul 15;21(14):3097-111. doi: 10.1093/hmg/dds132. Epub 2012, Apr 6. PMID:22492998 doi:http://dx.doi.org/10.1093/hmg/dds132
  5. ↑ Lieberman P. FOXP2 and Human Cognition. Cell. 2009 May 29;137(5):800-2. doi: 10.1016/j.cell.2009.05.013. PMID:19490887 doi:http://dx.doi.org/10.1016/j.cell.2009.05.013
  6. ↑ Passerini L, Santoni de Sio FR, Roncarolo MG, Bacchetta R. Forkhead box P3: the peacekeeper of the immune system. Int Rev Immunol. 2014 Mar;33(2):129-45. doi: 10.3109/08830185.2013.863303. Epub, 2013 Dec 19. PMID:24354325 doi:http://dx.doi.org/10.3109/08830185.2013.863303
  7. ↑ Sun T, Wang H, Li Q, Qian Z, Shen C. Forkhead box protein k1 recruits TET1 to act as a tumor suppressor and is associated with MRI detection. Jpn J Clin Oncol. 2016 Mar;46(3):209-21. doi: 10.1093/jjco/hyv185. Epub 2016 Jan , 4. PMID:26732382 doi:http://dx.doi.org/10.1093/jjco/hyv185
  8. ↑ Fan CL, Jiang J, Liu HC, Yang D. Forkhead box protein M1 predicts outcome in human osteosarcoma. Int J Clin Exp Med. 2015 Sep 15;8(9):15563-8. eCollection 2015. PMID:26629049
  9. ↑ Rogers JM, Waters CT, Seegar TCM, Jarrett SM, Hallworth AN, Blacklow SC, Bulyk ML. Bispecific Forkhead Transcription Factor FoxN3 Recognizes Two Distinct Motifs with Different DNA Shapes. Mol Cell. 2019 Feb 22. pii: S1097-2765(19)30039-5. doi:, 10.1016/j.molcel.2019.01.019. PMID:30826165 doi:http://dx.doi.org/10.1016/j.molcel.2019.01.019
  10. ↑ Zhu H. Forkhead box transcription factors in embryonic heart development and congenital heart disease. Life Sci. 2016 Jan 1;144:194-201. doi: 10.1016/j.lfs.2015.12.001. Epub 2015 Dec, 2. PMID:26656470 doi:http://dx.doi.org/10.1016/j.lfs.2015.12.001
  11. ↑ Cederberg A, Gronning LM, Ahren B, Tasken K, Carlsson P, Enerback S. FOXC2 is a winged helix gene that counteracts obesity, hypertriglyceridemia, and diet-induced insulin resistance. Cell. 2001 Sep 7;106(5):563-73. PMID:11551504
  12. ↑ Finegold DN, Kimak MA, Lawrence EC, Levinson KL, Cherniske EM, Pober BR, Dunlap JW, Ferrell RE. Truncating mutations in FOXC2 cause multiple lymphedema syndromes. Hum Mol Genet. 2001 May 15;10(11):1185-9. PMID:11371511

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, David Canner
Retrieved from "https://proteopedia.openfox.io/wiki/index.php?title=Forkhead_box_protein&oldid=3701803"