Twist-related protein 1

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.^[5][6]

TWIST1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2MJV
Identifiers
Aliases	TWIST1, twist family bHLH transcription factor 1, ACS3, BPES2, BPES3, CRS, CRS1, SCS, TWIST, bHLHa38, CSO, SWCOS
External IDs	OMIM: 601622; MGI: 98872; HomoloGene: 402; GeneCards: TWIST1; OMA:TWIST1 - orthologs
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p21.1 Start 19,020,991 bp[1] End 19,117,636 bp[1]
Gene location (Mouse) Chr. Chromosome 12 (mouse)[2] Band 12 A3|12 14.81 cM Start 34,007,670 bp[2] End 34,009,828 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in periodontal fiber mucosa of paranasal sinus oocyte buccal mucosa cell tendon of biceps brachii pericardium parietal pleura lactiferous duct placenta stromal cell of endometrium Top expressed in maxillary prominence mandibular prominence desmocranium hand genital tubercle allantois endocardial cushion dermis abdominal wall somatopleuric mesenchyme More reference expression data BioGPS More reference expression data
Gene ontology Molecular function DNA binding protein dimerization activity protein homodimerization activity protein domain specific binding DNA-binding transcription factor activity transcription factor binding bHLH transcription factor binding E-box binding protein binding protein heterodimerization activity DNA-binding transcription factor activity, RNA polymerase II-specific Cellular component nucleus nucleoplasm Biological process positive regulation of transcription regulatory region DNA binding embryonic skeletal system morphogenesis positive regulation of fatty acid beta-oxidation roof of mouth development cell differentiation positive regulation of cell motility regulation of transcription, DNA-templated negative regulation of molecular function ossification rhythmic process positive regulation of epithelial cell proliferation negative regulation of striated muscle tissue development regulation of bone mineralization aortic valve morphogenesis negative regulation of cell differentiation cardiac neural crest cell migration involved in outflow tract morphogenesis cellular response to growth factor stimulus positive regulation of monocyte chemotactic protein-1 production muscle organ development embryonic digit morphogenesis negative regulation of apoptotic process neuron migration in utero embryonic development negative regulation of transcription by RNA polymerase II outer ear morphogenesis eyelid development in camera-type eye mitral valve morphogenesis positive regulation of DNA-templated transcription, initiation positive regulation of epithelial to mesenchymal transition negative regulation of DNA-binding transcription factor activity transcription, DNA-templated negative regulation of osteoblast differentiation positive regulation of angiogenesis hindlimb morphogenesis negative regulation of phosphatidylinositol 3-kinase signaling cranial suture morphogenesis odontogenesis endocardial cushion morphogenesis negative regulation of double-strand break repair multicellular organism development cardiac neural crest cell development involved in outflow tract morphogenesis neural tube closure positive regulation of gene expression negative regulation of DNA damage response, signal transduction by p53 class mediator negative regulation of skeletal muscle tissue development embryonic limb morphogenesis negative regulation of oxidative phosphorylation uncoupler activity osteoblast differentiation positive regulation of tumor necrosis factor production cell proliferation involved in heart valve development embryonic cranial skeleton morphogenesis negative regulation of tumor necrosis factor production negative regulation of peroxisome proliferator activated receptor signaling pathway positive regulation of endocardial cushion to mesenchymal transition involved in heart valve formation negative regulation of histone acetylation embryonic camera-type eye formation bone development embryonic forelimb morphogenesis cellular response to hypoxia positive regulation of transcription by RNA polymerase II negative regulation of cellular senescence embryonic hindlimb morphogenesis negative regulation of transcription, DNA-templated cytokine-mediated signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7291 22160 Ensembl ENSG00000122691 ENSMUSG00000035799 UniProt Q15672 P26687 RefSeq (mRNA) NM_000474 NM_011658 RefSeq (protein) NP_000465 NP_035788 Location (UCSC) Chr 7: 19.02 – 19.12 Mb Chr 12: 34.01 – 34.01 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^[7]

Twist1 is thought to regulate osteogenic lineage.^[8]

Clinical significance

Mutations in the TWIST1 gene are associated with Saethre–Chotzen syndrome,^[9][10] breast cancer,^[11] and Sézary syndrome.^[12]

Craniosynostosis

TWIST1 mutations are involved in a number of craniosynostosis presentations. It can present in nonsyndromic forms (isolated scaphocephaly, right unicoronal synostosis, and turricephaly), but also in syndromic forms such as:^[13]

• Acrocephalosyndactyly type 1 (Apert syndrome) (primary FGFR2)
• Beare-Stevenson cutis gyrata syndrome (primary FGFR2)
• Crouzon syndrome (primary FGFR2)
• Crouzon syndrome-acanthosis nigricans syndrome (primary FGFR3)
• Jackson-Weiss syndrome (primary FGFR1 or FGFR2)
• Muenke syndrome (primary FGFR3)
• Pfeiffer syndrome (primary FGFR1 or FGFR2)

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.^[14] In cooperation with N-Myc, Twist-1 acts as an oncogene in several cancers including neuroblastoma.^[11][15]

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.^[14][16] Twist1 is extensively studied for its role in head- and neck cancers.^[17] 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.^[16][18] Moreover, Twist1 has been shown to be expressed under conditions of hypoxia, corresponding to the observation that hypoxic cells respond less to chemotherapeutic drugs.^[17]

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^[19] and inhibition of TIMP.^[20]

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.^[14]

Interactions

Twist transcription factor has been shown to interact with EP300,^[21] TCF3^[22] and PCAF.^[21]

See also

• Transcription factor
• TWIST2

References

1. GRCh38: Ensembl release 89: ENSG00000122691 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000035799 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Bourgeois P, Stoetzel C, Bolcato-Bellemin AL, Mattei MG, Perrin-Schmitt F (Dec 1996). "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. doi:10.1007/s003359900269. PMID 8995765. S2CID 42710079.
6. Dollfus H, Kumaramanickavel G, Biswas P, Stoetzel C, Quillet R, Denton M, Maw M, Perrin-Schmitt F (Jul 2001). "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. doi:10.1136/jmg.38.7.470. PMC 1757180. PMID 11474656.
7. "Entrez Gene: TWIST1 twist homolog 1 (acrocephalosyndactyly 3; Saethre–Chotzen syndrome) (Drosophila)".
8. Lee MS, Lowe GN, Strong DD, Wergedal JE, Glackin CA (Dec 1999). "TWIST, a basic helix–loop–helix transcription factor, can regulate the human osteogenic lineage". Journal of Cellular Biochemistry. 75 (4): 566–77. doi:10.1002/(SICI)1097-4644(19991215)75:4<566::AID-JCB3>3.0.CO;2-0. PMID 10572240. S2CID 21874692.
9. Kress W, Schropp C, Lieb G, Petersen B, Büsse-Ratzka M, Kunz J, Reinhart E, Schäfer WD, Sold J, Hoppe F, Pahnke J, Trusen A, Sörensen N, Krauss J, Collmann H (Jan 2006). "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. doi:10.1038/sj.ejhg.5201507. PMID 16251895.
10. Howard TD, Paznekas WA, Green ED, Chiang LC, Ma N, Ortiz de Luna RI, Garcia Delgado C, Gonzalez-Ramos M, Kline AD, Jabs EW (Jan 1997). "Mutations in TWIST, a basic helix-loop-helix transcription factor, in Saethre-Chotzen syndrome". Nature Genetics. 15 (1): 36–41. doi:10.1038/ng0197-36. PMID 8988166. S2CID 35360537.
11. Martin TA, Goyal A, Watkins G, Jiang WG (Jun 2005). "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. doi:10.1245/ASO.2005.04.010. PMID 15864483. S2CID 19102926.
12. van Doorn R, Dijkman R, Vermeer MH, Out-Luiting JJ, van der Raaij-Helmer EM, Willemze R, Tensen CP (Aug 2004). "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. doi:10.1158/0008-5472.CAN-04-1253. PMID 15313894. S2CID 6506412.
13. "TWIST1-related craniosynostosis (Concept Id: C4551902) - MedGen - NCBI". www.ncbi.nlm.nih.gov. Retrieved 2023-07-17.
14. Khan MA, Chen HC, Zhang D, Fu J (Oct 2013). "Twist: a molecular target in cancer therapeutics". Tumour Biology. 34 (5): 2497–506. doi:10.1007/s13277-013-1002-x. PMID 23873099. S2CID 498698.
15. Puisieux A, Valsesia-Wittmann S, Ansieau S (Jan 2006). "A twist for survival and cancer progression". British Journal of Cancer. 94 (1): 13–7. doi:10.1038/sj.bjc.6602876. PMC 2361066. PMID 16306876.
16. Roberts CM, Tran MA, Pitruzzello MC, Wen W, Loeza J, Dellinger TH, Mor G, Glackin CA (2016). "TWIST1 drives cisplatin resistance and cell survival in an ovarian cancer model, via upregulation of GAS6, L1CAM, and Akt signalling". Scientific Reports. 6: 37652. Bibcode:2016NatSR...637652R. doi:10.1038/srep37652. PMC 5120297. PMID 27876874.
17. Wu KJ, Yang MH (Dec 2011). "Epithelial-mesenchymal transition and cancer stemness: the Twist1-Bmi1 connection". Bioscience Reports. 31 (6): 449–55. doi:10.1042/BSR20100114. PMID 21919891. S2CID 16648243.
18. Zhuo WL, Wang Y, Zhuo XL, Zhang YS, Chen ZT (May 2008). "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. doi:10.1016/j.bbrc.2008.02.143. PMID 18331824.
19. Zhao XL, Sun T, Che N, Sun D, Zhao N, Dong XY, Gu Q, Yao Z, Sun BC (Mar 2011). "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. doi:10.1111/j.1582-4934.2010.01052.x. PMC 3922390. PMID 20219012.
20. Okamura H, Yoshida K, Haneji T (Jul 2009). "Negative regulation of TIMP1 is mediated by transcription factor TWIST1". International Journal of Oncology. 35 (1): 181–6. doi:10.3892/ijo_00000327. PMID 19513566.
21. Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (Feb 1999). "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell. 96 (3): 405–13. doi:10.1016/S0092-8674(00)80553-X. PMID 10025406. S2CID 15808193.
22. El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J (Mar 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–9. doi:10.1093/hmg/9.5.813. PMID 10749989.

Further reading

• Seto ML, Lee SJ, Sze RW, Cunningham ML (Dec 2001). "Another TWIST on Baller-Gerold syndrome". American Journal of Medical Genetics. 104 (4): 323–30. doi:10.1002/ajmg.10065. PMID 11754069.
• Brueton LA, van Herwerden L, Chotai KA, Winter RM (Oct 1992). "The mapping of a gene for craniosynostosis: evidence for linkage of the Saethre-Chotzen syndrome to distal chromosome 7p". Journal of Medical Genetics. 29 (10): 681–5. doi:10.1136/jmg.29.10.681. PMC 1016122. PMID 1433226.
• Bianchi DW, Cirillo-Silengo M, Luzzatti L, Greenstein RM (Jun 1981). "Interstitial deletion of the short arm of chromosome 7 without craniosynostosis". Clinical Genetics. 19 (6): 456–61. doi:10.1111/j.1399-0004.1981.tb02064.x. PMID 7296937. S2CID 25464482.
• Rose CS, King AA, Summers D, Palmer R, Yang S, Wilkie AO, Reardon W, Malcolm S, Winter RM (Aug 1994). "Localization of the genetic locus for Saethre-Chotzen syndrome to a 6 cM region of chromosome 7 using four cases with apparently balanced translocations at 7p21.2". Human Molecular Genetics. 3 (8): 1405–8. doi:10.1093/hmg/3.8.1405. PMID 7987323.
• Maw M, Kar B, Biswas J, Biswas P, Nancarrow D, Bridges R, Kumaramanickavel G, Denton M, Badrinath SS (Dec 1996). "Linkage of blepharophimosis syndrome in a large Indian pedigree to chromosome 7p". Human Molecular Genetics. 5 (12): 2049–54. doi:10.1093/hmg/5.12.2049. PMID 8968762.
• el Ghouzzi V, Le Merrer M, Perrin-Schmitt F, Lajeunie E, Benit P, Renier D, Bourgeois P, Bolcato-Bellemin AL, Munnich A, Bonaventure J (Jan 1997). "Mutations of the TWIST gene in the Saethre-Chotzen syndrome". Nature Genetics. 15 (1): 42–6. doi:10.1038/ng0197-42. PMID 8988167. S2CID 22140671.
• Wang SM, Coljee VW, Pignolo RJ, Rotenberg MO, Cristofalo VJ, Sierra F (Mar 1997). "Cloning of the human twist gene: its expression is retained in adult mesodermally-derived tissues". Gene. 187 (1): 83–92. doi:10.1016/S0378-1119(96)00727-5. PMID 9073070.
• Krebs I, Weis I, Hudler M, Rommens JM, Roth H, Scherer SW, Tsui LC, Füchtbauer EM, Grzeschik KH, Tsuji K, Kunz J (Jul 1997). "Translocation breakpoint maps 5 kb 3' from TWIST in a patient affected with Saethre-Chotzen syndrome". Human Molecular Genetics. 6 (7): 1079–86. doi:10.1093/hmg/6.7.1079. PMID 9215678.
• Rose CS, Patel P, Reardon W, Malcolm S, Winter RM (Aug 1997). "The TWIST gene, although not disrupted in Saethre-Chotzen patients with apparently balanced translocations of 7p21, is mutated in familial and sporadic cases". Human Molecular Genetics. 6 (8): 1369–73. doi:10.1093/hmg/6.8.1369. PMID 9259286.
• Hamamori Y, Wu HY, Sartorelli V, Kedes L (Nov 1997). "The basic domain of myogenic basic helix-loop-helix (bHLH) proteins is the novel target for direct inhibition by another bHLH protein, Twist". Molecular and Cellular Biology. 17 (11): 6563–73. doi:10.1128/mcb.17.11.6563. PMC 232510. PMID 9343420.
• Gripp KW, Stolle CA, Celle L, McDonald-McGinn DM, Whitaker LA, Zackai EH (Jan 1999). "TWIST gene mutation in a patient with radial aplasia and craniosynostosis: further evidence for heterogeneity of Baller-Gerold syndrome". American Journal of Medical Genetics. 82 (2): 170–6. doi:10.1002/(SICI)1096-8628(19990115)82:2<170::AID-AJMG14>3.0.CO;2-X. PMID 9934984.
• Hamamori Y, Sartorelli V, Ogryzko V, Puri PL, Wu HY, Wang JY, Nakatani Y, Kedes L (Feb 1999). "Regulation of histone acetyltransferases p300 and PCAF by the bHLH protein twist and adenoviral oncoprotein E1A". Cell. 96 (3): 405–13. doi:10.1016/S0092-8674(00)80553-X. PMID 10025406. S2CID 15808193.
• Kunz J, Hudler M, Fritz B (Aug 1999). "Identification of a frameshift mutation in the gene TWIST in a family affected with Robinow-Sorauf syndrome". Journal of Medical Genetics. 36 (8): 650–2. doi:10.1136/jmg.36.8.650. PMC 1762975. PMID 10465122.
• Maestro R, Dei Tos AP, Hamamori Y, Krasnokutsky S, Sartorelli V, Kedes L, Doglioni C, Beach DH, Hannon GJ (Sep 1999). "Twist is a potential oncogene that inhibits apoptosis". Genes & Development. 13 (17): 2207–17. doi:10.1101/gad.13.17.2207. PMC 317004. PMID 10485844.
• El Ghouzzi V, Legeai-Mallet L, Aresta S, Benoist C, Munnich A, de Gunzburg J, Bonaventure J (Mar 2000). "Saethre-Chotzen mutations cause TWIST protein degradation or impaired nuclear location". Human Molecular Genetics. 9 (5): 813–9. doi:10.1093/hmg/9.5.813. PMID 10749989.
• Lee MS, Lowe G, Flanagan S, Kuchler K, Glackin CA (Nov 2000). "Human Dermo-1 has attributes similar to twist in early bone development". Bone. 27 (5): 591–602. doi:10.1016/S8756-3282(00)00380-X. PMID 11062344.
• Dollfus H, Kumaramanickavel G, Biswas P, Stoetzel C, Quillet R, Denton M, Maw M, Perrin-Schmitt F (Jul 2001). "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. doi:10.1136/jmg.38.7.470. PMC 1757180. PMID 11474656.
• Elanko N, Sibbring JS, Metcalfe KA, Clayton-Smith J, Donnai D, Temple IK, Wall SA, Wilkie AO (Dec 2001). "A survey of TWIST for mutations in craniosynostosis reveals a variable length polyglycine tract in asymptomatic individuals". Human Mutation. 18 (6): 535–41. doi:10.1002/humu.1230. PMID 11748846. S2CID 45021510.
• Nurnberg ST, Guerraty MA, Wirka RC, Rao HS, Pjanic M, Norton S, et al. (January 2020). "Genomic profiling of human vascular cells identifies TWIST1 as a causal gene for common vascular diseases". PLOS Genetics. 16 (1): e1008538. doi:10.1371/journal.pgen.1008538. PMC 6975560. PMID 31917787.
• ZZhang J, Guo JR, Wu XL, Wang X, Zhu ZM, Wang Y, Gu X, Fan Y (March 2021). "TWIST1 induces phenotypic switching of vascular smooth muscle cells by downregulating p68 and microRNA-143/145". FEBS Open Bio. 11 (3): 932–943. doi:10.1002/2211-5463.13092. PMC 7931233. PMID 33470057.

External links

• GeneReviews/NCBI.NIH.UW entry on Saethre–Chotzen syndrome
• Twist+transcription+factor at the U.S. 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.