Biology:Twist transcription factor

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Short description: Transcription factor protein


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Twist-related protein 1 (TWIST1) also known as class A basic helix–loop–helix protein 38 (bHLHa38) is a basic helix-loop-helix transcription factor that in humans is encoded by the TWIST1 gene.[1][2]

Function

Basic helix-loop-helix (bHLH) transcription factors have been implicated in cell lineage determination and differentiation. The protein encoded by this gene is a bHLH transcription factor and shares similarity with another bHLH transcription factor, Dermo1 (a.k.a. TWIST2). The strongest expression of this mRNA is in placental tissue; in adults, mesodermally derived tissues express this mRNA preferentially.[3]

Twist1 is thought to regulate osteogenic lineage.[4]

Clinical significance

Mutations in the TWIST1 gene are associated with Saethre–Chotzen syndrome,[5][6] breast cancer,[7] and Sézary syndrome.[8]

As an oncogene

Twist plays an essential role in cancer metastasis. Over-expression of Twist or methylation of its promoter is common in metastatic carcinomas. Hence targeting Twist has a great promise as a cancer therapeutic.[9] In cooperation with N-Myc, Twist-1 acts as an oncogene in several cancers including neuroblastoma.[7][10]

Twist is activated by a variety of signal transduction pathways, including Akt, signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase, Ras, and Wnt signaling. Activated Twist upregulates N-cadherin and downregulates E-cadherin, which are the hallmarks of EMT. Moreover, Twist plays an important role in some physiological processes involved in metastasis, like angiogenesis, invadopodia, extravasation, and chromosomal instability. Twist also protects cancer cells from apoptotic cell death. In addition, Twist is responsible for the maintenance of cancer stem cells and the development of chemotherapy resistance.[9][11] Twist1 is extensively studied for its role in head- and neck cancers.[12] Here and in epithelial ovarian cancer, Twist1 has been shown to be involved in evading apoptosis, making the tumour cells resistant against platinum-based chemotherapeutic drugs like cisplatin.[11][13] Moreover, Twist1 has been shown to be expressed under conditions of hypoxia, corresponding to the observation that hypoxic cells respond less to chemotherapeutic drugs.[12]

Another process in which Twist 1 is involved is tumour metastasis. The underlying mechanism is not completely understood, but it has been implicated in the upregulation of matrix metalloproteinases[14] and inhibition of TIMP.[15]

Recently, targeting Twist has gained interest as a target for cancer therapeutics. The inactivation of Twist by small interfering RNA or chemotherapeutic approach has been demonstrated in vitro. Moreover, several inhibitors which are antagonistic to the upstream or downstream molecules of Twist signaling pathways have also been identified.[9]

Interactions

Twist transcription factor has been shown to interact with EP300,[16] TCF3[17] and PCAF.[16]

See also

References

  1. ↑ "The human H-twist gene is located at 7p21 and encodes a B-HLH protein that is 96% similar to its murine M-twist counterpart". Mammalian Genome 7 (12): 915–7. Dec 1996. doi:10.1007/s003359900269. PMID 8995765. 
  2. ↑ "Identification of a new TWIST mutation (7p21) with variable eyelid manifestations supports locus homogeneity of BPES at 3q22". Journal of Medical Genetics 38 (7): 470–2. Jul 2001. doi:10.1136/jmg.38.7.470. PMID 11474656. 
  3. ↑ "Entrez Gene: TWIST1 twist homolog 1 (acrocephalosyndactyly 3; Saethre–Chotzen syndrome) (Drosophila)". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=7291. 
  4. ↑ "TWIST, a basic helix–loop–helix transcription factor, can regulate the human osteogenic lineage". Journal of Cellular Biochemistry 75 (4): 566–77. Dec 1999. doi:10.1002/(SICI)1097-4644(19991215)75:4<566::AID-JCB3>3.0.CO;2-0. PMID 10572240. 
  5. ↑ "Saethre-Chotzen syndrome caused by TWIST 1 gene mutations: functional differentiation from Muenke coronal synostosis syndrome". European Journal of Human Genetics 14 (1): 39–48. Jan 2006. doi:10.1038/sj.ejhg.5201507. PMID 16251895. 
  6. ↑ "Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome". Nature Genetics 15 (1): 36–41. Jan 1997. doi:10.1038/ng0197-36. PMID 8988166. 
  7. ↑ 7.0 7.1 "Expression of the transcription factors snail, slug, and twist and their clinical significance in human breast cancer". Annals of Surgical Oncology 12 (6): 488–96. Jun 2005. doi:10.1245/ASO.2005.04.010. PMID 15864483. 
  8. ↑ "Aberrant expression of the tyrosine kinase receptor EphA4 and the transcription factor twist in Sézary syndrome identified by gene expression analysis". Cancer Research 64 (16): 5578–86. Aug 2004. doi:10.1158/0008-5472.CAN-04-1253. PMID 15313894. 
  9. ↑ 9.0 9.1 9.2 "Twist: a molecular target in cancer therapeutics". Tumour Biology 34 (5): 2497–506. Oct 2013. doi:10.1007/s13277-013-1002-x. PMID 23873099. 
  10. ↑ "A twist for survival and cancer progression". British Journal of Cancer 94 (1): 13–7. Jan 2006. doi:10.1038/sj.bjc.6602876. PMID 16306876. 
  11. ↑ 11.0 11.1 "TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling". Scientific Reports 6: 37652. 2016. doi:10.1038/srep37652. PMID 27876874. Bibcode: 2016NatSR...637652R. 
  12. ↑ 12.0 12.1 "Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection". Bioscience Reports 31 (6): 449–55. Dec 2011. doi:10.1042/BSR20100114. PMID 21919891. https://semanticscholar.org/paper/4f1806b0149f16ee407544599ffac24b21bb5ea7. 
  13. ↑ "Short interfering RNA directed against TWIST, a novel zinc finger transcription factor, increases A549 cell sensitivity to cisplatin via MAPK/mitochondrial pathway". Biochemical and Biophysical Research Communications 369 (4): 1098–102. May 2008. doi:10.1016/j.bbrc.2008.02.143. PMID 18331824. 
  14. ↑ "Promotion of hepatocellular carcinoma metastasis through matrix metalloproteinase activation by epithelial-mesenchymal transition regulator Twist1". Journal of Cellular and Molecular Medicine 15 (3): 691–700. Mar 2011. doi:10.1111/j.1582-4934.2010.01052.x. PMID 20219012. 
  15. ↑ "Negative regulation of TIMP1 is mediated by transcription factor TWIST1". International Journal of Oncology 35 (1): 181–6. Jul 2009. doi:10.3892/ijo_00000327. PMID 19513566. 
  16. ↑ 16.0 16.1 "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell 96 (3): 405–13. Feb 1999. doi:10.1016/S0092-8674(00)80553-X. PMID 10025406. 
  17. ↑ "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics 9 (5): 813–9. Mar 2000. doi:10.1093/hmg/9.5.813. PMID 10749989. 

Further reading

External links

This article incorporates text from the United States National Library of Medicine, which is in the public domain.




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