Structure-function analyses of the human SIX1-EYA2 complex reveal insights into metastasis and BOR syndrome

Nature Structural and Molecular Biology

Volumn 20, Issue 4, 2013, Pages 447-453

  Patrick, Aaron N ^a,b   Cabrera, Joshua H ^a   Smith, Anna L ^a   Chen, Xiaojiang S ^c   Ford, Heide L ^a,b   Zhao, Rui ^b  

^a UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF COLORADO   (United States)

^c UNIVERSITY OF SOUTHERN CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EYA2 PROTEIN; TRANSCRIPTION FACTOR; TRANSCRIPTION FACTOR SIX1; TRANSFORMING GROWTH FACTOR BETA; UNCLASSIFIED DRUG;

ARTICLE; BRANCHIOOTORENAL SYNDROME; CANCER GROWTH; DNA BINDING; EPITHELIAL MESENCHYMAL TRANSITION; GENE MUTATION; HUMAN; IN VIVO STUDY; METASTASIS; PHENOTYPE; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; PROTEIN STRUCTURE; SIGNAL TRANSDUCTION;

ANIMALS; BRANCHIO-OTO-RENAL SYNDROME; HOMEODOMAIN PROTEINS; HUMANS; INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS; MCF-7 CELLS; MICE; MICE, NUDE; MODELS, MOLECULAR; MUTATION, MISSENSE; NEOPLASM METASTASIS; NUCLEAR PROTEINS; PROTEIN TYROSINE PHOSPHATASES; STRUCTURE-ACTIVITY RELATIONSHIP;

MAMMALIA;

EID: 84876190366     PISSN: 15459993     EISSN: 15459985     Source Type: Journal    
DOI: 10.1038/nsmb.2505     Document Type: Article

References (59)

1. Christensen, K.L., Patrick, A.N., McCoy, E.L. & Ford, H.L. The six family of homeobox genes in development and cancer. Adv. Cancer Res. 101, 93-126 (2008).
2. Kawakami, K., Sato, S., Ozaki, H. & Ikeda, K. Six family genes-structure and function as transcription factors and their roles in development. Bioessays 22, 616-626 (2000).
3. Rebay, I., Silver, S.J. & Tootle, T.L. New vision from Eyes absent: transcription factors as enzymes. Trends Genet. 21, 163-171 (2005).
4. Li, X. et al. Eya protein phosphatase activity regulates Six1-Dach-Eya transcriptional effects in mammalian organogenesis. Nature 426, 247-254 (2003).
5. Tootle, T.L. et al. The transcription factor Eyes absent is a protein tyrosine phosphatase. Nature 426, 299-302 (2003).
6. Rayapureddi, J.P. et al. Eyes absent represents a class of protein tyrosine phosphatases. Nature 426, 295-298 (2003).
7. Jung, S.-K. et al. Crystal structure of ED-Eya2: insight into dual roles as a protein tyrosine phosphatase and a transcription factor. FASEB J. 24, 560-569 (2010).
8. Abdelhak, S. et al. A human homologue of the Drosophila eyes absent gene underlies branchio-oto-renal (BOR) syndrome and identifes a novel gene family. Nat. Genet. 15, 157-164 (1997).
9. Ruf, R.G. et al. SIX1 mutations cause branchio-oto-renal syndrome by disruption of EYA1-SIX1-DNA complexes. Proc. Natl. Acad. Sci. USA 101, 8090-8095 (2004).
10. Wayne, S. et al. Mutations in the transcriptional activator EYA4 cause late-onset deafness at the DFNA10 locus. Hum. Mol. Genet. 10, 195-200 (2001).
11. Zhang, Y., Knosp, B.M., Maconochie, M., Friedman, R.A. & Smith, R.J.H. A comparative study of Eya1 and Eya4 protein function and its implication in branchio-oto-renal syndrome and DFNA10. J. Assoc. Res. Otolaryngol. 5, 295-304 (2004).
12. Schönberger, J. et al. Mutation in the transcriptional coactivator EYA4 causes dilated cardiomyopathy and sensorineural hearing loss. Nat. Genet. 37, 418-422 (2005).
13. Delgado-Olguín, P. et al. Epigenetic repression of cardiac progenitor gene expression by Ezh2 is required for postnatal cardiac homeostasis. Nat. Genet. 44, 343-347 (2012).
14. Ford, H.L., Kabingu, E.N., Bump, E.A., Mutter, G.L. & Pardee, A.B. Abrogation of the G2 cell cycle checkpoint associated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis. Proc. Natl. Acad. Sci. USA 95, 12608-12613 (1998).
15. Yu, Y. et al. Expression profling identifes the cytoskeletal organizer ezrin and the developmental homeoprotein Six-1 as key metastatic regulators. Nat. Med. 10, 175-181 (2004).
16. Micalizzi, D.S. et al. The Six1 homeoprotein induces human mammary carcinoma cells to undergo epithelial-mesenchymal transition and metastasis in mice through increasing TGF-β signaling. J. Clin. Invest. 119, 2678-2690 (2009).
17. Mimae, T. et al. Upregulation of Notch2 and Six1 is associated with progression of early-stage lung adenocarcinoma and a more aggressive phenotype at advanced stages. Clin. Cancer Res. 18, 945-955 (2012).
18. Zheng, X.-H. et al. Expression and clinical implications of homeobox gene Six1 in cervical cancer cell lines and cervical epithelial tissues. Int. J. Gynecol. Cancer 20, 1587-1592 (2010).
19. Ng, K.T. et al. Clinicopathological signifcance of homeoprotein Six1 in hepatocellular carcinoma. Br. J. Cancer 95, 1050-1055 (2006).
20. Ono, H. et al. SIX1 promotes epithelial-mesenchymal transition in colorectal cancer through ZEB1 activation. Oncogene 31, 4923-4934 (2012).
21. Behbakht, K. et al. Six1 overexpression in ovarian carcinoma causes resistance to TRAIL-mediated apoptosis and is associated with poor survival. Cancer Res. 67, 3036-3042 (2007).
22. McCoy, E.L. et al. Six1 expands the mouse mammary epithelial stem/progenitor cell pool and induces mammary tumors that undergo epithelial-mesenchymal transition. J. Clin. Invest. 119, 2663-2677 (2009).
23. Iwanaga, R. et al. Expression of Six1 in luminal breast cancers predicts poor prognosis and promotes increases in tumor initiating cells by activation of extracellular signal-regulated kinase and transforming growth factor-β signaling pathways. Breast Cancer Res. 14, R100 (2012).
24. Wang, C.-A. et al. SIX1 induces lymphangiogenesis and metastasis via upregulation of VEGF-C in mouse models of breast cancer. J. Clin. Invest. 122, 1895-1906 (2012).
25. Ng, K.T.P. et al. Suppression of tumorigenesis and metastasis of hepatocellular carcinoma by shRNA interference targeting on homeoprotein Six1. Int. J. Cancer 127, 859-872 (2010).
26. Darnell, J.E. Transcription factors as targets for cancer therapy. Nat. Rev. Cancer 2, 740-749 (2002).
27. Li, C.M. et al. Gene expression in Wilms' tumor mimics the earliest committed stage in the metanephric mesenchymal-epithelial transition. Am. J. Pathol. 160, 2181-2190 (2002).
28. Wang, Q.-F. et al. MLL fusion proteins preferentially regulate a subset of wild-type MLL target genes in the leukemic genome. Blood 117, 6895-6905 (2011).
29. Miller, S.J. et al. Inhibition of Eyes Absent Homolog 4 expression induces malignant peripheral nerve sheath tumor necrosis. Oncogene 29, 368-379 (2010).
30. Zhang, L. et al. Transcriptional coactivator Drosophila eyes absent homologue 2 is up-regulated in epithelial ovarian cancer and promotes tumor growth. Cancer Res. 65, 925-932 (2005).
31. Farabaugh, S.M., Micalizzi, D.S., Jedlicka, P., Zhao, R. & Ford, H.L. Eya2 is required to mediate the pro-metastatic functions of Six1 via the induction of TGF-β signaling, epithelial-mesenchymal transition, and cancer stem cell properties. Oncogene 31, 552-562 (2012).
32. Pandey, R.N. et al. The Eyes Absent phosphatase-transactivator proteins promote proliferation, transformation, migration, and invasion of tumor cells. Oncogene 29, 3715-3722 (2010).
33. Moon, A.F., Mueller, G.A., Zhong, X. & Pedersen, L.C. A synergistic approach to protein crystallization: combination of a fxed-arm carrier with surface entropy reduction. Protein Sci. 19, 901-913 (2010).
34. Holm, L. & Sander, C. Protein structure comparison by alignment of distance matrices. J. Mol. Biol. 233, 123-138 (1993).
35. Ades, S.E. & Sauer, R.T. Specifcity of minor-groove and major-groove interactions in a homeodomain-DNA complex. Biochemistry 34, 14601-14608 (1995).
36. Hu, S., Mamedova, A. & Hegde, R.S. DNA-binding and regulation mechanisms of the SIX family of retinal determination proteins. Biochemistry 47, 3586-3594 (2008).
37. Percival-Smith, A., Müller, M., Affolter, M. & Gehring, W.J. The interaction with DNA of wild-type and mutant fushi tarazu homeodomains. EMBO J. 9, 3967-3974 (1990).
38. Shang, Z. et al. Design of a 'minimAl' homeodomain: the N-terminal arm modulates DNA binding affnity and stabilizes homeodomain structure. Proc. Natl. Acad. Sci. USA 91, 8373-8377 (1994).
39. Liu, Y. et al. Discovery, optimization and validation of an optimal DNA-binding sequence for the Six1 homeodomain transcription factor. Nucleic Acids Res. 40, 8227-8239 (2012).
40. Kawakami, K., Ohto, H., Ikeda, K. & Roeder, R.G. Structure, function and expression of a murine homeobox protein AREC3, a homologue of Drosophila sine oculis gene product, and implication in development. Nucleic Acids Res. 24, 303-310 (1996).
41. Harris, S.E., Winchester, C.L. & Johnson, K.J. Functional analysis of the homeodomain protein SIX5. Nucleic Acids Res. 28, 1871-1878 (2000).
42. Patrick, A.N., Schiemann, B.J., Yang, K., Zhao, R. & Ford, H.L. Biochemical and functional characterization of six SIX1 Branchio-oto-renal syndrome mutations. J. Biol. Chem. 284, 20781-20790 (2009).
43. Kussie, P.H. et al. Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274, 948-953 (1996).
44. Sattler, M. et al. Structure of Bcl-xL-Bak peptide complex: recognition between regulators of apoptosis. Science 275, 983-986 (1997).
45. Vassilev, L.T. et al. In vivo activation of the p53 pathway by small-molecule antagonists of MDM2. Science 303, 844-848 (2004).
46. Tse, C. et al. ABT-263: a potent and orally bioavailable Bcl-2 family inhibitor. Cancer Res. 68, 3421-3428 (2008).
47. Azuma, N., Hirakiyama, A., Inoue, T., Asaka, A. & Yamada, M. Mutations of a human homologue of the Drosophila eyes absent gene (EYA1) detected in patients with congenital cataracts and ocular anterior segment anomalies. Hum. Mol. Genet. 9, 363-366 (2000).
48. Orten, D.J. et al. Branchio-oto-renal syndrome (BOR): novel mutations in the EYA1 gene, and a review of the mutational genetics of BOR. Hum. Mutat. 29, 537-544 (2008).
49. Krug, P. et al. Mutation screening of the EYA1, SIX1, and SIX5 genes in a large cohort of patients harboring branchio-oto-renal syndrome calls into question the pathogenic role of SIX5 mutations. Hum. Mutat. 32, 183-190 (2011).
50. Bonini, N.M., Bui, Q.T., Gray-Board, G.L. & Warrick, J.M. The Drosophila eyes absent gene directs ectopic eye formation in a pathway conserved between fies and vertebrates. Development 124, 4819-4826 (1997).
51. Bui, Q.T., Zimmerman, J.E., Liu, H. & Bonini, N.M. Molecular analysis of Drosophila eyes absent mutants reveals features of the conserved Eya domain. Genetics 155, 709-720 (2000).
52. Grifone, R. et al. Eya1 and Eya2 proteins are required for hypaxial somitic myogenesis in the mouse embryo. Dev. Biol. 302, 602-616 (2007).
53. Worth, C.L., Preissner, R. & Blundell, T.L. SDM-a server for predicting effects of mutations on protein stability and malfunction. Nucleic Acids Res. 39, W215-W222 (2011).
54. Buller, C., Xu, X., Marquis, V., Schwanke, R. & Xu, P.X. Molecular effects of Eya1 domain mutations causing organ defects in BOR syndrome. Hum. Mol. Genet. 10, 2775-2781 (2001).
55. Mutsuddi, M. et al. Using Drosophila to decipher how mutations associated with human branchio-oto-renal syndrome and optical defects compromise the protein tyrosine phosphatase and transcriptional functions of eyes absent. Genetics 170, 687-695 (2005).
56. Rayapureddi, J.P. & Hegde, R.S. Branchio-oto-renal syndrome associated mutations in Eyes Absent 1 result in loss of phosphatase activity. FEBS Lett. 580, 3853-3859 (2006).
57. Ikeda, K., Watanabe, Y., Ohto, H. & Kawakami, K. Molecular interaction and synergistic activation of a promoter by Six, Eya, and Dach proteins mediated through CREB binding protein. Mol. Cell Biol. 22, 6759-6766 (2002).
58. Wrana, J.L. et al. TGF β signals through a heteromeric protein kinase receptor complex. Cell 71, 1003-1014 (1992).
59. Drasin, D.J., Robin, T.P. & Ford, H.L. Breast cancer epithelial-to-mesenchymal transition: examining the functional consequences of plasticity. Breast Cancer Res. 13, 226 (2011).