Crystal structure of EML1 reveals the basis for Hsp90 dependence of oncogenic EML4-ALK by disruption of an atypical β-propeller domain

Proceedings of the National Academy of Sciences of the United States of America

Volumn 111, Issue 14, 2014, Pages 5195-5200

  Richards, Mark W ^a   P Law, Edward W ^a   Rennalls, La'verne P ^b   Busacca, Sara ^a   O'Regan, Laura ^a   Fry, Andrew M ^a   Fennell, Dean A ^a   Bayliss, Richard ^a  

^a UNIVERSITY OF LEICESTER   (United Kingdom)

^b INSTITUTE OF CANCER RESEARCH   (United Kingdom)

Author keywords

Stratified medicine; Structural biology

Indexed keywords

ALPHA TUBULIN; ANAPLASTIC LYMPHOMA KINASE; BETA TUBULIN; BORTEZOMIB; CASPASE 3; CASPASE 7; ECHINODERM MICROTUBULE ASSOCIATED LIKE PROTEIN 4; GANETESPIB; HYBRID PROTEIN; INTERLEUKIN 3; MICROTUBULE ASSOCIATED PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; UNCLASSIFIED DRUG;

ANIMAL CELL; APOPTOSIS; ARTICLE; CELL SURVIVAL; CELL VIABILITY; CONTROLLED STUDY; CRYSTAL STRUCTURE; GENETIC VARIABILITY; INSECT CELL; LUNG NON SMALL CELL CANCER; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; PROTEIN SECONDARY STRUCTURE; SPODOPTERA FRUGIPERDA; TAPE DOMAIN;

STRATIFIED MEDICINE; STRUCTURAL BIOLOGY;

AMINO ACID SEQUENCE; CELL CYCLE PROTEINS; CRYSTALLOGRAPHY, X-RAY; HSP90 HEAT-SHOCK PROTEINS; HUMANS; MICROTUBULE-ASSOCIATED PROTEINS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; PROTEIN CONFORMATION; RECEPTOR PROTEIN-TYROSINE KINASES; SEQUENCE HOMOLOGY, AMINO ACID; SERINE ENDOPEPTIDASES;

EID: 84898027006     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1322892111     Document Type: Article

References (31)

1. Soda M, et al. (2007) Identification of the transforming EML4-ALK fusion gene in nonsmall-cell lung cancer. Nature 448(7153):561-566.
2. Sasaki T, Rodig SJ, Chirieac LR, Jänne PA (2010) The biology and treatment of EML4-ALK non-small cell lung cancer. Eur J Cancer 46(10):1773-1780.
3. De Keersmaecker K, et al. (2005) Fusion of EML1 to ABL1 in T-cell acute lymphoblastic leukemia with cryptic t(9;14)(q34;q32). Blood 105(12):4849-4852.
4. Choi YL, et al. (2008) Identification of novel isoforms of the EML4-ALK transforming gene in non-small cell lung cancer. Cancer Res 68(13):4971-4976.
5. Takezawa K, Okamoto I, Nishio K, Jänne PA, Nakagawa K (2011) Role of ERK-BIM and STAT3-survivin signaling pathways in ALK inhibitor-induced apoptosis in EML4-ALKpositive lung cancer. Clin Cancer Res 17(8):2140-2148.
6. Choi YL, et al.; ALK Lung Cancer Study Group (2010) EML4-ALK mutations in lung cancer that confer resistance to ALK inhibitors. N Engl J Med 363(18):1734-1739.
7. Katayama R, et al. (2011) Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci USA 108(18):7535-7540.
8. Neckers L, Workman P (2012) Hsp90 molecular chaperone inhibitors: Are we there yet? Clin Cancer Res 18(1):64-76.
9. Normant E, et al. (2011) The Hsp90 inhibitor IPI-504 rapidly lowers EML4-ALK levels and induces tumor regression in ALK-driven NSCLC models. Oncogene 30(22):2581-2586.
10. Sang J, et al. (2013) Targeted inhibition of the molecular chaperone Hsp90 overcomes ALK inhibitor resistance in non-small cell lung cancer. Cancer Discov 3(4):430-443.
11. Sequist LV, et al. (2010) Activity of IPI-504, a novel heat-shock protein 90 inhibitor, in patients with molecularly defined non-small-cell lung cancer. J Clin Oncol 28(33): 4953-4960.
12. Heuckmann JM, et al. (2012) Differential protein stability and ALK inhibitor sensitivity of EML4-ALK fusion variants. Clin Cancer Res 18(17):4682-4690.
13. Suprenant KA, Dean K, McKee J, Hake S (1993) EMAP, an echinoderm microtubuleassociated protein found in microtubule-ribosome complexes. J Cell Sci 104(2):445-450.
14. Hamill DR, Howell B, Cassimeris L, Suprenant KA (1998) Purification of a WD repeat protein, EMAP, that promotes microtubule dynamics through an inhibition of rescue. J Biol Chem 273(15):9285-9291.
15. Eichenmuller B, Everley P, Palange J, Lepley D, Suprenant KA (2002) The human EMAP-like protein-70 (ELP70) is a microtubule destabilizer that localizes to the mitotic apparatus. J Biol Chem 277(2):1301-1309.
16. Lepley DM, Palange JM, Suprenant KA (1999) Sequence and expression patterns of a human EMAP-related protein-2 (HuEMAP-2). Gene 237(2):343-349.
17. Tegha-Dunghu J, et al. (2008) EML3 is a nuclear microtubule-binding protein required for the correct alignment of chromosomes in metaphase. J Cell Sci 121(Pt 10): 1718-1726.
18. Pollmann M, et al. (2006) Human EML4, a novel member of the EMAP family, is essential for microtubule formation. Exp Cell Res 312(17):3241-3251.
19. Suprenant KA, et al. (2000) Conservation of the WD-repeat, microtubule-binding protein, EMAP, in sea urchins, humans, and the nematode C. elegans. Dev Genes Evol 210(1):2-10.
20. Hueston JL, et al. (2008) The C. elegans EMAP-like protein, ELP-1 is required for touch sensation and associates with microtubules and adhesion complexes. BMC Dev Biol 8(110):110.
21. Mohri K, Vorobiev S, Fedorov AA, Almo SC, Ono S (2004) Identification of functional residues on Caenorhabditis elegans actin-interacting protein 1 (UNC-78) for disassembly of actin depolymerizing factor/cofilin-bound actin filaments. J Biol Chem 279(30):31697-31707.
22. Voegtli WC, Madrona AY, Wilson DK (2003) The structure of Aip1p, a WD repeat protein that regulates Cofilin-mediated actin depolymerization. J Biol Chem 278(36): 34373-34379.
23. Ying W, et al. (2012) Ganetespib, a unique triazolone-containing Hsp90 inhibitor, exhibits potent antitumor activity and a superior safety profile for cancer therapy. Mol Cancer Ther 11(2):475-484.
24. Hegyi H, Buday L, Tompa P (2009) Intrinsic structural disorder confers cellular viability on oncogenic fusion proteins. PLOS Comput Biol 5(10):e1000552.
25. Chen Z, et al. (2010) Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene. Cancer Res 70(23):9827-9836.
26. Zhang X, et al. (2010) Fusion of EML4 and ALK is associated with development of lung adenocarcinomas lacking EGFR and KRAS mutations and is correlated with ALK expression. Mol Cancer 9:188.
27. Thunnissen E, et al. (2012) EML4-ALK testing in non-small cell carcinomas of the lung: A review with recommendations. Virchows Arch 461(3):245-257.
28. Collaborative Computational Project, Number 4 (1994) The CCP4 suite: Programs for protein crystallography. Acta Crystallogr D Biol Crystallogr 50(Pt 5):760-763.
29. Adams PD, et al. (2002) PHENIX: Building new software for automated crystallographic structure determination. Acta Crystallogr D Biol Crystallogr 58(Pt 11): 1948-1954.
30. Emsley P, Cowtan K (2004) Coot: Model-building tools for molecular graphics. Acta Crystallogr D Biol Crystallogr 60(Pt 12):2126-2132.
31. Chen VB, et al. (2010) MolProbity: All-atom structure validation for macromolecular crystallography. Acta Crystallogr D Biol Crystallogr 66(Pt 1):12-21.