Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Minuesa, Gerard; Albanese, Steven K.; Xie, Wei; Kazansky, Yaniv; Worroll, Daniel; Chow, Arthur; Schurer, Alexandra; Park, Sun-Mi; Rotsides, Christina Z.; Taggart, James; Rizzi, Andrea; Naden, Levi N.; Chou, Timothy; Gourkanti, Saroj; Cappel, Daniel; Passarelli, Maria C.; Fairchild, Lauren; Adura, Carolina; Glickman, J. Fraser; Schulman, Jessica; Famulare, Christopher; Patel, Minal; Eibl, Joseph K.; Ross, Gregory M.; Bhattacharya, Shibani; Tan, Derek S.; Leslie, Christina S.; Beuming, Thijs; Patel, Dinshaw J.; Goldgur, Yehuda; Chodera, John D.; Kharas, Michael G.

doi:10.1038/s41467-019-10523-3

Title: Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia

Journal Article · 19 June 2019 · Nature Communications

DOI: https://doi.org/10.1038/s41467-019-10523-3 · OSTI ID:1561312

Minuesa, Gerard ^[1];

^[1];

^[1]; Kazansky, Yaniv ^[2];

^[3]; Chow, Arthur ^[1]; Schurer, Alexandra ^[1]; Park, Sun-Mi ^[1]; Rotsides, Christina Z. ^[1]; Taggart, James ^[1];

^[4]; Naden, Levi N. ^[1]; Chou, Timothy ^[1]; Gourkanti, Saroj ^[1];

^[5]; Passarelli, Maria C. ^[6]; Fairchild, Lauren ^[4]; Adura, Carolina ^[7]; Glickman, J. Fraser ^[7]; Schulman, Jessica ^[1] more »

Memorial Sloan Kettering Cancer Center, New York, NY (United States)
Cornell Univ., Ithaca, NY (United States). Weill Medical College; Rockefeller Univ., New York, NY (United States); Memorial Sloan Kettering Cancer Center, New York, NY (United States). Sloan Kettering Institute
Cornell Univ., Ithaca, NY (United States). Weill Cornell Graduate School of Medical Sciences
Memorial Sloan Kettering Cancer Center, New York, NY (United States); Cornell Univ., Ithaca, NY (United States). Weill Medical College
Schrodinger GmbH, Manheim (Germany)
Memorial Sloan Kettering Cancer Center, New York, NY (United States); Cornell Univ., Ithaca, NY (United States). Weill Medical College; Rockefeller Univ., New York, NY (United States)
Rockefeller Univ., New York, NY (United States)
Northern Ontario School of Medicine, Sudbury, ON (Canada)
New York Structural Biology Center, New York, NY (United States)
Memorial Sloan Kettering Cancer Center, New York, NY (United States). Sloan Kettering Institute
Schrodinger Inc., New York, NY (United States)

The MUSASHI (MSI) family of RNA binding proteins (MSI1 and MSI2) contribute to a wide spectrum of cancers including acute myeloid leukemia. We find that the small molecule Ro 08–2750 (Ro) binds directly and selectively to MSI2 and competes for its RNA binding in biochemical assays. Ro treatment in mouse and human myeloid leukemia cells results in an increase in differentiation and apoptosis, inhibition of known MSI-targets, and a shared global gene expression signature similar to shRNA depletion of MSI2. Ro demonstrates in vivo inhibition of c-MYC and reduces disease burden in a murine AML leukemia model. Thus, we identify a small molecule that targets MSI’s oncogenic activity. Our study provides a framework for targeting RNA binding proteins in cancer.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States). Advanced Photon Source (APS)

Sponsoring Organization:: USDOE; National Institutes of Health (NIH); Commonwealth Foundation for Cancer Research; Memorial Sloan Kettering Cancer Center

Grant/Contract Number:: AC02–06CH11357; NIDDK NIH R01-DK101989–01A1; NCI 1R01CA193842–01; P30 CA08748; R01 GM121505; T32GM007739; T32 CA062948-Gudas; P30-CA008748; P41GM103403; HEI-S10RR029205; CO6RR015495

OSTI ID:: 1561312

Journal Information:: Nature Communications, Vol. 10, Issue 1; ISSN 2041-1723

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: ENGLISH

References (112)

Discovery of a Small-Molecule Inhibitor of Protein–MicroRNA Interaction Using Binding Assay with a Site-Specifically Labeled Lin28 Lim, Donghyun; Byun, Wan Gi; Koo, Ja Young Journal of the American Chemical Society, Vol. 138, Issue 41 https://doi.org/10.1021/jacs.6b06965	journal	October 2016
Musashi 2 contributes to the stemness and chemoresistance of liver cancer stem cells via LIN28A activation Fang, Tian; Lv, Hongwei; Wu, Fuquan Cancer Letters, Vol. 384 https://doi.org/10.1016/j.canlet.2016.10.007	journal	January 2017
Expression of the Musashi1 gene encoding the RNA-binding protein in human hepatoma cell lines Shu, Hong-Jin; Saito, Takafumi; Watanabe, Hisayoshi Biochemical and Biophysical Research Communications, Vol. 293, Issue 1 https://doi.org/10.1016/S0006-291X(02)00175-4	journal	April 2002
Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia Kwon, Hyog Young; Bajaj, Jeevisha; Ito, Takahiro Cell Stem Cell, Vol. 17, Issue 2 https://doi.org/10.1016/j.stem.2015.06.006	journal	August 2015
Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR Meisner, Nicole-Claudia; Hintersteiner, Martin; Mueller, Kurt Nature Chemical Biology, Vol. 3, Issue 8 https://doi.org/10.1038/nchembio.2007.14	journal	July 2007
Cancerous stem cells can arise from pediatric brain tumors Hemmati, H. D.; Nakano, I.; Lazareff, J. A. Proceedings of the National Academy of Sciences, Vol. 100, Issue 25 https://doi.org/10.1073/pnas.2036535100	journal	November 2003
Transformation of the intestinal epithelium by the MSI2 RNA-binding protein Wang, Shan; Li, Ning; Yousefi, Maryam Nature Communications, Vol. 6, Issue 1 https://doi.org/10.1038/ncomms7517	journal	March 2015
A novel TTC40–MSI2 fusion in de novo acute myeloid leukemia with an unbalanced 10;17 translocation Saleki, Reza; Christensen, Todd; Liu, Weihua Leukemia & Lymphoma, Vol. 56, Issue 4 https://doi.org/10.3109/10428194.2014.947611	journal	August 2014
Prediction of Protein–Ligand Binding Poses via a Combination of Induced Fit Docking and Metadynamics Simulations Clark, Anthony J.; Tiwary, Pratyush; Borrelli, Ken Journal of Chemical Theory and Computation, Vol. 12, Issue 6 https://doi.org/10.1021/acs.jctc.6b00201	journal	May 2016
Automatic atom type and bond type perception in molecular mechanical calculations Wang, Junmei; Wang, Wei; Kollman, Peter A. Journal of Molecular Graphics and Modelling, Vol. 25, Issue 2 https://doi.org/10.1016/j.jmgm.2005.12.005	journal	October 2006
MSI2 is required for maintaining activated myelodysplastic syndrome stem cells Taggart, James; Ho, Tzu-Chieh; Amin, Elianna Nature Communications, Vol. 7, Issue 1 https://doi.org/10.1038/ncomms10739	journal	February 2016
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia Kharas, Michael G.; Lengner, Christopher J.; Al-Shahrour, Fatima Nature Medicine, Vol. 16, Issue 8 https://doi.org/10.1038/nm.2187	journal	July 2010
Therapeutic targeting of splicing in cancer Lee, Stanley Chun-Wei; Abdel-Wahab, Omar Nature Medicine, Vol. 22, Issue 9 https://doi.org/10.1038/nm.4165	journal	September 2016
Cooperation of Musashi-2, Numb, MDM2, and P53 in drug resistance and malignant biology of pancreatic cancer Sheng, Weiwei; Dong, Ming; Chen, Chuanping The FASEB Journal, Vol. 31, Issue 6 https://doi.org/10.1096/fj.201601240R	journal	June 2017
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Spectroscopic and Calorimetric Studies on the Binding of Alkaloids Berberine, Palmatine and Coralyne to Double Stranded RNA Polynucleotides Islam, Md. Maidul; Chowdhury, Sebanti Roy; Kumar, Gopinatha Suresh The Journal of Physical Chemistry B, Vol. 113, Issue 4 https://doi.org/10.1021/jp806597w	journal	January 2009
Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway Zhang, Huijuan; Tan, Shi; Wang, Juan Experimental Cell Research, Vol. 320, Issue 1 https://doi.org/10.1016/j.yexcr.2013.09.009	journal	January 2014
Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia Thol, Felicitas; Winschel, Claudia; Sonntag, Ann-Kathrin Annals of Hematology, Vol. 92, Issue 3 https://doi.org/10.1007/s00277-012-1637-5	journal	December 2012
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs Park, Sun-Mi; Deering, Raquel P.; Lu, Yuheng The Journal of Experimental Medicine, Vol. 211, Issue 1 https://doi.org/10.1084/jem.20130736	journal	January 2014
Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles Subramanian, A.; Tamayo, P.; Mootha, V. K. Proceedings of the National Academy of Sciences, Vol. 102, Issue 43, p. 15545-15550 https://doi.org/10.1073/pnas.0506580102	journal	September 2005
Musashi2 sustains the mixed-lineage leukemia–driven stem cell regulatory program Park, Sun-Mi; Gönen, Mithat; Vu, Ly Journal of Clinical Investigation, Vol. 125, Issue 3 https://doi.org/10.1172/JCI78440	journal	February 2015
Improved methods for building protein models in electron density maps and the location of errors in these models Jones, T. A.; Zou, J. Y.; Cowan, S. W. Acta Crystallographica Section A Foundations of Crystallography, Vol. 47, Issue 2, p. 110-119 https://doi.org/10.1107/S0108767390010224	journal	March 1991
Natural product (−)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1 Lan, Lan; Appelman, Carl; Smith, Amber R. Molecular Oncology, Vol. 9, Issue 7 https://doi.org/10.1016/j.molonc.2015.03.014	journal	April 2015
RNA-Binding Protein Musashi2: Developmentally Regulated Expression in Neural Precursor Cells and Subpopulations of Neurons in Mammalian CNS Sakakibara, Shin-ichi; Nakamura, Yuki; Satoh, Hitoshi The Journal of Neuroscience, Vol. 21, Issue 20 https://doi.org/10.1523/JNEUROSCI.21-20-08091.2001	journal	October 2001
The Msi Family of RNA-Binding Proteins Function Redundantly as Intestinal Oncoproteins Li, Ning; Yousefi, Maryam; Nakauka-Ddamba, Angela Cell Reports, Vol. 13, Issue 11 https://doi.org/10.1016/j.celrep.2015.11.022	journal	December 2015
Studies on Succinate Dehydrogenase. Site of Attachment of the Covalently-Bound Flavin to the Peptide Chain Salach, Jim; Walker, Wolfram H.; Singer, Thomas P. European Journal of Biochemistry, Vol. 26, Issue 2 https://doi.org/10.1111/j.1432-1033.1972.tb01765.x	journal	March 1972
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells Rentas, Stefan; Holzapfel, Nicholas T.; Belew, Muluken S. Nature, Vol. 532, Issue 7600 https://doi.org/10.1038/nature17665	journal	April 2016
Development and testing of a general amber force field Wang, Junmei; Wolf, Romain M.; Caldwell, James W. Journal of Computational Chemistry, Vol. 25, Issue 9 https://doi.org/10.1002/jcc.20035	journal	January 2004
Natural Product Gossypol and its Derivatives in Precision Cancer Medicine Zeng, Yun; Ma, Jingwen; Xu, Liang Current Medicinal Chemistry, Vol. 26, Issue 10 https://doi.org/10.2174/0929867324666170523123655	journal	June 2019
A Simple Method for Automated Equilibration Detection in Molecular Simulations Chodera, John D. Journal of Chemical Theory and Computation, Vol. 12, Issue 4 https://doi.org/10.1021/acs.jctc.5b00784	journal	March 2016
MSMBuilder2: Modeling Conformational Dynamics on the Picosecond to Millisecond Scale Beauchamp, Kyle A.; Bowman, Gregory R.; Lane, Thomas J. Journal of Chemical Theory and Computation, Vol. 7, Issue 10 https://doi.org/10.1021/ct200463m	journal	August 2011
Fast, efficient generation of high-quality atomic charges. AM1-BCC model: I. Method Jakalian, Araz; Bush, Bruce L.; Jack, David B. Journal of Computational Chemistry, Vol. 21, Issue 2 https://doi.org/10.1002/(SICI)1096-987X(20000130)21:2<132::AID-JCC5>3.0.CO;2-P	journal	January 2000
MSI2 protein expression predicts unfavorable outcome in acute myeloid leukemia Byers, Richard J.; Currie, Treeve; Tholouli, Eleni Blood, Vol. 118, Issue 10 https://doi.org/10.1182/blood-2011-04-346767	journal	September 2011
MDTraj: A Modern Open Library for the Analysis of Molecular Dynamics Trajectories McGibbon, Robert T.; Beauchamp, Kyle A.; Harrigan, Matthew P. Biophysical Journal, Vol. 109, Issue 8 https://doi.org/10.1016/j.bpj.2015.08.015	journal	October 2015
Protein and ligand preparation: parameters, protocols, and influence on virtual screening enrichments Madhavi Sastry, G.; Adzhigirey, Matvey; Day, Tyler Journal of Computer-Aided Molecular Design, Vol. 27, Issue 3 https://doi.org/10.1007/s10822-013-9644-8	journal	March 2013
Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand binding Young, Tom; Abel, Robert; Kim, Byungchan Proceedings of the National Academy of Sciences, Vol. 104, Issue 3 https://doi.org/10.1073/pnas.0610202104	journal	January 2007
Novel Procedure for Modeling Ligand/Receptor Induced Fit Effects Sherman, Woody; Day, Tyler; Jacobson, Matthew P. Journal of Medicinal Chemistry, Vol. 49, Issue 2 https://doi.org/10.1021/jm050540c	journal	January 2006
Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation Choo, A. Y.; Yoon, S. -O.; Kim, S. G. Proceedings of the National Academy of Sciences, Vol. 105, Issue 45 https://doi.org/10.1073/pnas.0809136105	journal	October 2008
Musashi RNA-Binding Proteins as Cancer Drivers and Novel Therapeutic Targets Kudinov, Alexander E.; Karanicolas, John; Golemis, Erica A. Clinical Cancer Research, Vol. 23, Issue 9 https://doi.org/10.1158/1078-0432.CCR-16-2728	journal	January 2017
Particle mesh Ewald: An N ⋅log( N ) method for Ewald sums in large systems Darden, Tom; York, Darrin; Pedersen, Lee The Journal of Chemical Physics, Vol. 98, Issue 12 https://doi.org/10.1063/1.464397	journal	June 1993
RNA-Binding Proteins in Cancer: Old Players and New Actors Pereira, Bruno; Billaud, Marc; Almeida, Raquel Trends in Cancer, Vol. 3, Issue 7 https://doi.org/10.1016/j.trecan.2017.05.003	journal	July 2017
Identifying and Characterizing Binding Sites and Assessing Druggability Halgren, Thomas A. Journal of Chemical Information and Modeling, Vol. 49, Issue 2 https://doi.org/10.1021/ci800324m	journal	January 2009
Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity Kanemura, Yonehiro; Yamasaki, M.; Mori, Kanji Differentiation, Vol. 68, Issue 2-3 https://doi.org/10.1046/j.1432-0436.2001.680208.x	journal	October 2001
Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer Kang, M-H; Jeong, K. J.; Kim, W. Y. Oncogene, Vol. 36, Issue 12 https://doi.org/10.1038/onc.2016.327	journal	September 2016
Regulation of myeloid leukaemia by the cell-fate determinant Musashi Ito, Takahiro; Kwon, Hyog Young; Zimdahl, Bryan Nature, Vol. 466, Issue 7307 https://doi.org/10.1038/nature09171	journal	July 2010
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB Maier, James A.; Martinez, Carmenza; Kasavajhala, Koushik Journal of Chemical Theory and Computation, Vol. 11, Issue 8 https://doi.org/10.1021/acs.jctc.5b00255	journal	July 2015
Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions Ohyama, Takako; Nagata, Takashi; Tsuda, Kengo Nucleic Acids Research, Vol. 40, Issue 7 https://doi.org/10.1093/nar/gkr1139	journal	December 2011
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma Fox, Raymond G.; Lytle, Nikki K.; Jaquish, Dawn V. Nature, Vol. 534, Issue 7607 https://doi.org/10.1038/nature17988	journal	June 2016
EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22 De Weer, A.; Speleman, F.; Cauwelier, B. Haematologica, Vol. 93, Issue 12 https://doi.org/10.3324/haematol.13192	journal	September 2008
Allosteric inhibition of a stem cell RNA-binding protein by an intermediary metabolite Clingman, Carina C.; Deveau, Laura M.; Hay, Samantha A. eLife, Vol. 3 https://doi.org/10.7554/eLife.02848	journal	June 2014
Efficient molecular dynamics using geodesic integration and solvent–solute splitting Leimkuhler, Benedict; Matthews, Charles Proceedings of the Royal Society A: Mathematical, Physical and Engineering Sciences, Vol. 472, Issue 2189 https://doi.org/10.1098/rspa.2016.0138	journal	May 2016
A brave new world of RNA-binding proteins Hentze, Matthias W.; Castello, Alfredo; Schwarzl, Thomas Nature Reviews Molecular Cell Biology, Vol. 19, Issue 5 https://doi.org/10.1038/nrm.2017.130	journal	January 2018
A 1536-Well Fluorescence Polarization Assay to Screen for Modulators of the MUSASHI Family of RNA-Binding Proteins Minuesa, Gerard; Antczak, Christophe; Shum, David Combinatorial Chemistry & High Throughput Screening, Vol. 17, Issue 7 https://doi.org/10.2174/1386207317666140609122714	journal	July 2014
Replica exchange and expanded ensemble simulations as Gibbs sampling: Simple improvements for enhanced mixing Chodera, John D.; Shirts, Michael R. The Journal of Chemical Physics, Vol. 135, Issue 19 https://doi.org/10.1063/1.3660669	journal	November 2011
Flavin Recognition by an RNA Aptamer Targeted toward FAD ^† Roychowdhury-Saha, Manami; Lato, Susan M.; Shank, Eric D. Biochemistry, Vol. 41, Issue 8 https://doi.org/10.1021/bi015719d	journal	February 2002
Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer Wang, Xiao-Yang; Yu, Huina; Linnoila, R. Ilona Oncotarget, Vol. 4, Issue 5 https://doi.org/10.18632/oncotarget.1034	journal	May 2013
Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias Wang, K.; Sanchez-Martin, M.; Wang, X. Leukemia, Vol. 31, Issue 1 https://doi.org/10.1038/leu.2016.166	journal	June 2016
Statistically optimal analysis of samples from multiple equilibrium states Shirts, Michael R.; Chodera, John D. The Journal of Chemical Physics, Vol. 129, Issue 12 https://doi.org/10.1063/1.2978177	journal	September 2008
Identification of novel pyrazoloquinazolinecarboxilate analogues to inhibit nerve growth factor in vitro Eibl, Joseph K.; Strasser, Bridget C.; Ross, Gregory M. European Journal of Pharmacology, Vol. 708, Issue 1-3 https://doi.org/10.1016/j.ejphar.2013.03.029	journal	May 2013
Anticancer sulfonamides target splicing by inducing RBM39 degradation via recruitment to DCAF15 Han, Ting; Goralski, Maria; Gaskill, Nicholas Science, Vol. 356, Issue 6336 https://doi.org/10.1126/science.aal3755	journal	March 2017
Determination of Alkali and Halide Monovalent Ion Parameters for Use in Explicitly Solvated Biomolecular Simulations Joung, In Suk; Cheatham, Thomas E. The Journal of Physical Chemistry B, Vol. 112, Issue 30 https://doi.org/10.1021/jp8001614	journal	July 2008
Functional screen of MSI2 interactors identifies an essential role for SYNCRIP in myeloid leukemia stem cells Vu, Ly P.; Prieto, Camila; Amin, Elianna M. Nature Genetics, Vol. 49, Issue 6 https://doi.org/10.1038/ng.3854	journal	April 2017
Stem Cells, Cancer, and MUSASHI in Blood and Guts Kharas, Michael G.; Lengner, Christopher J. Trends in Cancer, Vol. 3, Issue 5 https://doi.org/10.1016/j.trecan.2017.03.007	journal	May 2017
The Novel KLF4/MSI2 Signaling Pathway Regulates Growth and Metastasis of Pancreatic Cancer Guo, Kun; Cui, Jiujie; Quan, Ming Clinical Cancer Research, Vol. 23, Issue 3 https://doi.org/10.1158/1078-0432.CCR-16-1064	journal	July 2016
Breast cancer cells produce tenascin C as a metastatic niche component to colonize the lungs Oskarsson, Thordur; Acharyya, Swarnali; Zhang, Xiang H-F Nature Medicine, Vol. 17, Issue 7 https://doi.org/10.1038/nm.2379	journal	June 2011
[20] Processing of X-ray diffraction data collected in oscillation mode Otwinowski, Zbyszek; Minor, Wladek Macromolecular Crystallography Part A, 307-326 https://doi.org/10.1016/S0076-6879(97)76066-X	book	January 1997
Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics Wang, Kai; Chodera, John D.; Yang, Yanzhi Journal of Computer-Aided Molecular Design, Vol. 27, Issue 12 https://doi.org/10.1007/s10822-013-9689-8	journal	December 2013
A Conserved Three-nucleotide Core Motif Defines Musashi RNA Binding Specificity Zearfoss, N. Ruth; Deveau, Laura M.; Clingman, Carina C. Journal of Biological Chemistry, Vol. 289, Issue 51 https://doi.org/10.1074/jbc.M114.597112	journal	November 2014
OpenMM 7: Rapid development of high performance algorithms for molecular dynamics Eastman, Peter; Swails, Jason; Chodera, John D. PLOS Computational Biology, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pcbi.1005659	journal	July 2017
Development and testing of a general amber force field Wang, Junmei; Wolf, Romain M.; Caldwell, James W. Journal of Computational Chemistry, Vol. 25, Issue 9 https://doi.org/10.1002/jcc.20035	journal	January 2004
Prognostic significance of expression levels of stem cell regulators MSI2 and NUMB in acute myeloid leukemia Thol, Felicitas; Winschel, Claudia; Sonntag, Ann-Kathrin Annals of Hematology, Vol. 92, Issue 3 https://doi.org/10.1007/s00277-012-1637-5	journal	December 2012
Identifying ligand binding sites and poses using GPU-accelerated Hamiltonian replica exchange molecular dynamics Wang, Kai; Chodera, John D.; Yang, Yanzhi Journal of Computer-Aided Molecular Design, Vol. 27, Issue 12 https://doi.org/10.1007/s10822-013-9689-8	journal	December 2013
Natural product (−)-gossypol inhibits colon cancer cell growth by targeting RNA-binding protein Musashi-1 Lan, Lan; Appelman, Carl; Smith, Amber R. Molecular Oncology, Vol. 9, Issue 7 https://doi.org/10.1016/j.molonc.2015.03.014	journal	April 2015
Tetraspanin 3 Is Required for the Development and Propagation of Acute Myelogenous Leukemia Kwon, Hyog Young; Bajaj, Jeevisha; Ito, Takahiro Cell Stem Cell, Vol. 17, Issue 2 https://doi.org/10.1016/j.stem.2015.06.006	journal	August 2015
Stem Cells, Cancer, and MUSASHI in Blood and Guts Kharas, Michael G.; Lengner, Christopher J. Trends in Cancer, Vol. 3, Issue 5 https://doi.org/10.1016/j.trecan.2017.03.007	journal	May 2017
Musashi2 modulates K562 leukemic cell proliferation and apoptosis involving the MAPK pathway Zhang, Huijuan; Tan, Shi; Wang, Juan Experimental Cell Research, Vol. 320, Issue 1 https://doi.org/10.1016/j.yexcr.2013.09.009	journal	January 2014
ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB Maier, James A.; Martinez, Carmenza; Kasavajhala, Koushik Journal of Chemical Theory and Computation, Vol. 11, Issue 8 https://doi.org/10.1021/acs.jctc.5b00255	journal	July 2015
A Simple Method for Automated Equilibration Detection in Molecular Simulations Chodera, John D. Journal of Chemical Theory and Computation, Vol. 12, Issue 4 https://doi.org/10.1021/acs.jctc.5b00784	journal	March 2016
Prediction of Protein–Ligand Binding Poses via a Combination of Induced Fit Docking and Metadynamics Simulations Clark, Anthony J.; Tiwary, Pratyush; Borrelli, Ken Journal of Chemical Theory and Computation, Vol. 12, Issue 6 https://doi.org/10.1021/acs.jctc.6b00201	journal	May 2016
Flavin Recognition by an RNA Aptamer Targeted toward FAD ^† Roychowdhury-Saha, Manami; Lato, Susan M.; Shank, Eric D. Biochemistry, Vol. 41, Issue 8 https://doi.org/10.1021/bi015719d	journal	February 2002
Identifying and Characterizing Binding Sites and Assessing Druggability Halgren, Thomas A. Journal of Chemical Information and Modeling, Vol. 49, Issue 2 https://doi.org/10.1021/ci800324m	journal	January 2009
MSMBuilder2: Modeling Conformational Dynamics on the Picosecond to Millisecond Scale Beauchamp, Kyle A.; Bowman, Gregory R.; Lane, Thomas J. Journal of Chemical Theory and Computation, Vol. 7, Issue 10 https://doi.org/10.1021/ct200463m	journal	August 2011
Glide: A New Approach for Rapid, Accurate Docking and Scoring. 2. Enrichment Factors in Database Screening Halgren, Thomas A.; Murphy, Robert B.; Friesner, Richard A. Journal of Medicinal Chemistry, Vol. 47, Issue 7 https://doi.org/10.1021/jm030644s	journal	March 2004
Novel Procedure for Modeling Ligand/Receptor Induced Fit Effects Sherman, Woody; Day, Tyler; Jacobson, Matthew P. Journal of Medicinal Chemistry, Vol. 49, Issue 2 https://doi.org/10.1021/jm050540c	journal	January 2006
Spectroscopic and Calorimetric Studies on the Binding of Alkaloids Berberine, Palmatine and Coralyne to Double Stranded RNA Polynucleotides Islam, Md. Maidul; Chowdhury, Sebanti Roy; Kumar, Gopinatha Suresh The Journal of Physical Chemistry B, Vol. 113, Issue 4 https://doi.org/10.1021/jp806597w	journal	January 2009
Patient-derived xenotransplants can recapitulate the genetic driver landscape of acute leukemias Wang, K.; Sanchez-Martin, M.; Wang, X. Leukemia, Vol. 31, Issue 1 https://doi.org/10.1038/leu.2016.166	journal	June 2016
Regulation of myeloid leukaemia by the cell-fate determinant Musashi Ito, Takahiro; Kwon, Hyog Young; Zimdahl, Bryan Nature, Vol. 466, Issue 7307 https://doi.org/10.1038/nature09171	journal	July 2010
Musashi-2 attenuates AHR signalling to expand human haematopoietic stem cells Rentas, Stefan; Holzapfel, Nicholas T.; Belew, Muluken S. Nature, Vol. 532, Issue 7600 https://doi.org/10.1038/nature17665	journal	April 2016
Image-based detection and targeting of therapy resistance in pancreatic adenocarcinoma Fox, Raymond G.; Lytle, Nikki K.; Jaquish, Dawn V. Nature, Vol. 534, Issue 7607 https://doi.org/10.1038/nature17988	journal	June 2016
Identification and mechanistic characterization of low-molecular-weight inhibitors for HuR Meisner, Nicole-Claudia; Hintersteiner, Martin; Mueller, Kurt Nature Chemical Biology, Vol. 3, Issue 8 https://doi.org/10.1038/nchembio.2007.14	journal	July 2007
Musashi-2 regulates normal hematopoiesis and promotes aggressive myeloid leukemia Kharas, Michael G.; Lengner, Christopher J.; Al-Shahrour, Fatima Nature Medicine, Vol. 16, Issue 8 https://doi.org/10.1038/nm.2187	journal	July 2010
Therapeutic targeting of splicing in cancer Lee, Stanley Chun-Wei; Abdel-Wahab, Omar Nature Medicine, Vol. 22, Issue 9 https://doi.org/10.1038/nm.4165	journal	September 2016
A brave new world of RNA-binding proteins Hentze, Matthias W.; Castello, Alfredo; Schwarzl, Thomas Nature Reviews Molecular Cell Biology, Vol. 19, Issue 5 https://doi.org/10.1038/nrm.2017.130	journal	January 2018
Musashi RNA-binding protein 2 regulates estrogen receptor 1 function in breast cancer Kang, M-H; Jeong, K. J.; Kim, W. Y. Oncogene, Vol. 36, Issue 12 https://doi.org/10.1038/onc.2016.327	journal	September 2016
A novel specific PERK activator reduces toxicity and extends survival in Huntington's disease models Ganz, Javier; Shacham, Talya; Kramer, Maria Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-63899-4	journal	April 2020
Mir34a constrains pancreatic carcinogenesis Hidalgo-Sastre, Ana; Lubeseder-Martellato, Clara; Engleitner, Thomas Scientific Reports, Vol. 10, Issue 1 https://doi.org/10.1038/s41598-020-66561-1	journal	June 2020
Musashi1, an evolutionarily conserved neural RNA-binding protein, is a versatile marker of human glioma cells in determining their cellular origin, malignancy, and proliferative activity Kanemura, Yonehiro; Yamasaki, M.; Mori, Kanji Differentiation, Vol. 68, Issue 2-3 https://doi.org/10.1046/j.1432-0436.2001.680208.x	journal	October 2001
Comparison of simple potential functions for simulating liquid water Jorgensen, William L.; Chandrasekhar, Jayaraman; Madura, Jeffry D. The Journal of Chemical Physics, Vol. 79, Issue 2 https://doi.org/10.1063/1.445869	journal	July 1983
Motifs for molecular recognition exploiting hydrophobic enclosure in protein–ligand binding Young, Tom; Abel, Robert; Kim, Byungchan Proceedings of the National Academy of Sciences, Vol. 104, Issue 3 https://doi.org/10.1073/pnas.0610202104	journal	January 2007
Rapamycin differentially inhibits S6Ks and 4E-BP1 to mediate cell-type-specific repression of mRNA translation Choo, A. Y.; Yoon, S. -O.; Kim, S. G. Proceedings of the National Academy of Sciences, Vol. 105, Issue 45 https://doi.org/10.1073/pnas.0809136105	journal	October 2008
Cancerous stem cells can arise from pediatric brain tumors Hemmati, H. D.; Nakano, I.; Lazareff, J. A. Proceedings of the National Academy of Sciences, Vol. 100, Issue 25 https://doi.org/10.1073/pnas.2036535100	journal	November 2003
Musashi-2 controls cell fate, lineage bias, and TGF-β signaling in HSCs Park, Sun-Mi; Deering, Raquel P.; Lu, Yuheng The Journal of Experimental Medicine, Vol. 211, Issue 1 https://doi.org/10.1084/jem.20130736	journal	January 2014
Structure of Musashi1 in a complex with target RNA: the role of aromatic stacking interactions Ohyama, Takako; Nagata, Takashi; Tsuda, Kengo Nucleic Acids Research, Vol. 40, Issue 7 https://doi.org/10.1093/nar/gkr1139	journal	December 2011
The Oncogenic RNA-Binding Protein Musashi1 Is Regulated by HuR via mRNA Translation and Stability in Glioblastoma Cells Vo, D. T.; Abdelmohsen, K.; Martindale, J. L. Molecular Cancer Research, Vol. 10, Issue 1 https://doi.org/10.1158/1541-7786.mcr-11-0208	journal	January 2012
Essential role of the RNA-binding protein HuR in progenitor cell survival in mice Ghosh, Mallika; Aguila, Hector Leonardo; Michaud, Jason Journal of Clinical Investigation, Vol. 119, Issue 12 https://doi.org/10.1172/jci38263	journal	December 2009
OpenMM 7: Rapid development of high performance algorithms for molecular dynamics Eastman, Peter; Swails, Jason; Chodera, John D. PLOS Computational Biology, Vol. 13, Issue 7 https://doi.org/10.1371/journal.pcbi.1005659	journal	July 2017
The Lactate Dehydrogenase Inhibitor Gossypol Inhibits Radiation-Induced Pulmonary Fibrosis Judge, Jennifer L.; Lacy, Shannon H.; Ku, Wei-Yao Radiation Research, Vol. 188, Issue 1 https://doi.org/10.1667/rr14620.1	journal	July 2017
Musashi1 as a potential therapeutic target and diagnostic marker for lung cancer Wang, Xiao-Yang; Yu, Huina; Linnoila, R. Ilona Oncotarget, Vol. 4, Issue 5 https://doi.org/10.18632/oncotarget.1034	journal	May 2013
A 1536-Well Fluorescence Polarization Assay to Screen for Modulators of the MUSASHI Family of RNA-Binding Proteins Minuesa, Gerard; Antczak, Christophe; Shum, David Combinatorial Chemistry & High Throughput Screening, Vol. 17, Issue 7 https://doi.org/10.2174/1386207317666140609122714	journal	July 2014
A novel TTC40–MSI2 fusion in de novo acute myeloid leukemia with an unbalanced 10;17 translocation Saleki, Reza; Christensen, Todd; Liu, Weihua Leukemia & Lymphoma, Vol. 56, Issue 4 https://doi.org/10.3109/10428194.2014.947611	journal	August 2014
EVI1 overexpression in t(3;17) positive myeloid malignancies results from juxtaposition of EVI1 to the MSI2 locus at 17q22 De Weer, A.; Speleman, F.; Cauwelier, B. Haematologica, Vol. 93, Issue 12 https://doi.org/10.3324/haematol.13192	journal	September 2008
Replica exchange and expanded ensemble simulations as Gibbs sampling: Simple improvements for enhanced mixing Chodera, John D.; Shirts, Michael R. arXiv https://doi.org/10.48550/arxiv.1105.5749	text	January 2011

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Correction to: Musashi2 promotes EGF-induced EMT in pancreatic cancer via ZEB1-ERK/MAPK signaling Sheng, Weiwei; Shi, Xiaoyang; Lin, Yiheng Journal of Experimental & Clinical Cancer Research, Vol. 39, Issue 1 https://doi.org/10.1186/s13046-020-01663-2	journal	August 2020

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