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Decrypting lysine deacetylase inhibitor action and protein modifications by dose-resolved proteomics

Chang, Yun Chien (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Gnann, Christian (författare)
KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab
Steimbach, Raphael R. (författare)
Cancer Drug Development, German Cancer Research Center (DKFZ), Heidelberg, Baden-Wurttemberg, Germany, Baden-Württemberg; Biosciences Faculty, Heidelberg University, Heidelberg, Baden-Wurttemberg, Germany, Baden-Württemberg
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Bayer, Florian P. (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Lechner, Severin (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Sakhteman, Amirhossein (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Abele, Miriam (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria; Bavarian Center for Biomolecular Mass Spectrometry (BayBioMS), TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Zecha, Jana (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Trendel, Jakob (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
The, Matthew (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria
Käller Lundberg, Emma (författare)
KTH,Cellulär och klinisk proteomik,Science for Life Laboratory, SciLifeLab,Department of Bioengineering, Stanford University, Stanford, CA, USA; Department of Pathology, Stanford University, Stanford, CA, USA
Miller, Aubry K. (författare)
Cancer Drug Development, German Cancer Research Center (DKFZ), Heidelberg, Baden-Wurttemberg, Germany, Baden-Württemberg; German Cancer Consortium (DKTK), Heidelberg, Baden-Wurttemberg, Germany, Baden-Württemberg
Kuster, Bernhard (författare)
Chair of Proteomics and Bioanalytics, TUM School of Life Sciences, Technical University of Munich, Freising, Bavaria, Germany, Bavaria; German Cancer Consortium (DKTK), Partner Site Munich and German Cancer Research Center (DKFZ), Heidelberg, Baden-Wurttemberg, Germany, Baden-Württemberg
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 (creator_code:org_t)
Elsevier BV, 2024
2024
Engelska.
Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 43:6
Relaterad länk:
https://doi.org/10.1...
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https://urn.kb.se/re...
https://doi.org/10.1...
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  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
Stäng  
  • Lysine deacetylase inhibitors (KDACis) are approved drugs for cutaneous T cell lymphoma (CTCL), peripheral T cell lymphoma (PTCL), and multiple myeloma, but many aspects of their cellular mechanism of action (MoA) and substantial toxicity are not well understood. To shed more light on how KDACis elicit cellular responses, we systematically measured dose-dependent changes in acetylation, phosphorylation, and protein expression in response to 21 clinical and pre-clinical KDACis. The resulting 862,000 dose-response curves revealed, for instance, limited cellular specificity of histone deacetylase (HDAC) 1, 2, 3, and 6 inhibitors; strong cross-talk between acetylation and phosphorylation pathways; localization of most drug-responsive acetylation sites to intrinsically disordered regions (IDRs); an underappreciated role of acetylation in protein structure; and a shift in EP300 protein abundance between the cytoplasm and the nucleus. This comprehensive dataset serves as a resource for the investigation of the molecular mechanisms underlying KDACi action in cells and can be interactively explored online in ProteomicsDB.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

Nyckelord

acetylation
chemical proteomics
CP: Molecular biology
HDACs
lysine deacetylase inhibitors
mass spectrometry
phosphorylation
proteomic pharmacology

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