Small molecule inhibitors and CRISPR/Cas9 mutagenesis demonstrate that SMYD2 and SMYD3 activity are dispensable for autonomous cancer cell proliferation

Autor:	Cuyue Tang, Michael John Munchhof, Kat Cosmopoulos, Kip A. West, Mikel P. Moyer, Sherri Smith, Lorna Helen Mitchell, Margaret Porter Scott, Haris Jahic, Alexandra R. Grassian, Megan Alene Cloonan Foley, Thomas V. Riera, Darren Martin Harvey, Scott Ribich, P. Ann Boriack-Sjodin, Kevin Wayne Kuntz, Nigel J. Waters, Dorothy Brach, Christine Klaus, J. Joshua Smith, Robert A. Copeland, Trupti Lingaraj, Elizabeth A. Admirand, Jennifer Totman, Michael Thomenius, Christina R. Majer, Tim J. Wigle, Richard Chesworth, Alejandra Raimondi, Jodi Gureasko, Nathalie Rioux, James Edward John Mills, Suzanne L. Jacques, William P. Janzen
Rok vydání:	2017
Předmět:	0301 basic medicine Methyltransferase Carcinogenesis lcsh:Medicine Biochemistry Synthetic Genome Editing Genome Engineering RNA interference Medicine and Health Sciences CRISPR Enzyme Inhibitors lcsh:Science Multidisciplinary Organic Compounds Chemical Reactions Crispr Small molecule Phenotype Enzymes Chemistry Oncology Cell Processes Physical Sciences Engineering and Technology RNA Interference Synthetic Biology Research Article Biotechnology Mutagenesis (molecular biology technique) Adenocarcinoma of Lung Bioengineering Computational biology Biology Methylation Small Molecule Libraries 03 medical and health sciences Humans Cell Proliferation Cell growth Cas9 lcsh:R Organic Chemistry Chemical Compounds Biology and Life Sciences Proteins Histone-Lysine N-Methyltransferase Methyltransferases Cell Biology Synthetic Genomics 030104 developmental biology A549 Cells Synthetic Bioengineering Small Molecules Enzymology lcsh:Q CRISPR-Cas Systems
Zdroj:	PLoS ONE PLoS ONE, Vol 13, Iss 6, p e0197372 (2018)
ISSN:	1932-6203
Popis:	A key challenge in the development of precision medicine is defining the phenotypic consequences of pharmacological modulation of specific target macromolecules. To address this issue, a variety of genetic, molecular and chemical tools can be used. All of these approaches can produce misleading results if the specificity of the tools is not well understood and the proper controls are not performed. In this paper we illustrate these general themes by providing detailed studies of small molecule inhibitors of the enzymatic activity of two members of the SMYD branch of the protein lysine methyltransferases, SMYD2 and SMYD3. We show that tool compounds as well as CRISPR/Cas9 fail to reproduce many of the cell proliferation findings associated with SMYD2 and SMYD3 inhibition previously obtained with RNAi based approaches and with early stage chemical probes.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::db6179ff168da8f29fc3b07b8965b83d https://pubmed.ncbi.nlm.nih.gov/29856759 Zobrazit plný text záznamu