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12 results on '"M Kool"'

2. Targeting the interaction of HDAC2 and MYC in Group 3 medulloblastoma

Author

Till Milde, Martina Schnölzer, Andreas E. Kulozik, M Kool, SM Pfister, Olaf Witt, S Brabetz, Ina Oehme, Uwe Warnken, Florian Selt, Jonas Ecker, and Robert J. Wechsler-Reya

Subjects
Medulloblastoma, Gene knockdown, Histone deacetylase 2, Protein degradation, Biology, medicine.disease, Molecular biology, chemistry.chemical_compound, chemistry, Cell culture, Pediatrics, Perinatology and Child Health, MG132, Proteasome inhibitor, medicine, Transcription factor, medicine.drug
Abstract

Patients with high-risk subgroup medulloblastoma (MB) show poor overall survival rates despite aggressive treatment while survivors suffer from important treatment-associated morbidity. Particularly poor outcome is observed in patients with tumors of the molecular subgroup Group 3 with an amplification and high levels of the transcription factor MYC. We have previously shown that Group 3 MB cell lines with MYC amplification are highly susceptible to pan- and class I-histone deacetylase (HDAC) inhibitor treatment. We here explore the molecular interaction of the well known oncogenic driver MYC and class I HDAC2. Six established MB cell lines were used for experiments in cell culture, including MYC amplified cell lines. The functional interaction between MYC and HDAC2 was investigated by enzymatic inhibition of class I HDACs using class I-selective HDAC inhibitors (HDACi) and by siRNA-mediated knockdown of HDAC2. Observed protein degradation was rescued with proteasome inhibition using small molecule proteasome inhibitor MG132. The direct interaction of HDAC2 and MYC was analyzed in co-immunoprecipitation and mass spectrometry studies. The pharmacological inhibition of class I HDACs including HDAC2 as well as artificial HDAC2 protein depletion lead to reduced MYC protein levels, most likely due to increased proteasomal degradation. MYC and HDAC2 are localized in a protein complex together with other potential drug targets. Our data suggest that class I HDAC inhibition leads to destabilization of MYC protein depriving the cells from one of their main oncogenic drivers. The MYC/HDAC2 multi-protein complex represents an attractive target for novel combinatorial treatment approaches. Funding: MYCNet (BMBF Germany), Verein fur krebskranke Kinder Odenwald e.V.

Published
2016
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7. Targeting differentially expressed histone deacetylases in Medulloblastoma – novel approach for treatment of high risk patients

Author

Ralph Mazitschek, Hedwig E. Deubzer, Jonas Ecker, Andreas E. Kulozik, M Lodrini, Olaf Witt, Andrey Korshunov, Till Milde, A. von Deimling, M Kool, Ina Oehme, S Pfister, and A Schomburg

Subjects
Medulloblastoma, Histone, High risk patients, biology, Pediatrics, Perinatology and Child Health, medicine, biology.protein, medicine.disease, Bioinformatics
Published
2013
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10. Targeting PLK1 and Aurora kinases in medulloblastoma

Author

Thorsten Pietsch, Rogier Versteeg, Stefan Rutkowski, Ellen M. Westerhout, Steve Clifford, M Holst, H.N. Caron, and M Kool

Subjects
Medulloblastoma, Kinase, Pediatrics, Perinatology and Child Health, Immunology, medicine, Cancer research, Biology, medicine.disease, PLK1
Published
2012
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11. Molecular subtypes in medulloblastoma: an International meta-analysis for profiles, genetic aberrations, clinicopathological features AND SURVIVAL

Author

Scott L. Pomeroy, Michael D. Taylor, David W. Ellison, Yoon Jae Cho, S Pfister, A von Buehren, Hendrik Witt, Stefan Rutkowski, François Doz, Olivier Delattre, M Remke, M Kool, Rogier Versteeg, Richard J. Gilbertson, Thorsten Pietsch, Thomas Hielscher, A. Y. N. Schouten-van Meeteren, Steve Clifford, Jan Koster, Paul A. Northcott, Christine Haberler, and Andrey Korshunov

Subjects
Oncology, Medulloblastoma, medicine.medical_specialty, Pathology, business.industry, Meta-analysis, Internal medicine, Pediatrics, Perinatology and Child Health, Medicine, Clinicopathological features, Gene deletion, business, medicine.disease
Published
2011
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12. The KidsCancerKinome - Validation of Drug Targets for High Risk Childhood Cancers

Author

Katia Scotlandi, M Holst, Gilles Vassal, Rob Pieters, H.N. Caron, Thorsten Pietsch, B Geoerger, Steve Clifford, C Lanvers, Ellen M. Westerhout, M Kool, Stefanie Segers, O Degrand, M L den Boer, Peter Stroeken, J Shipley, Olivier Delattre, Jan J. Molenaar, Rogier Versteeg, Jane Renshaw, R Warps, M Serra, M Benetkiewicz, and Arnauld Verschuur

Subjects
Drug, Oncology, medicine.medical_specialty, business.industry, media_common.quotation_subject, Internal medicine, Pediatrics, Perinatology and Child Health, medicine, business, media_common
Published
2010
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