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Title: A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation
Authors: Chen, E.W. 
Tay, N.Q. 
Brzostek, J. 
Gascoigne, N.R.J. 
Rybakin, V. 
Keywords: Cdc7
T cell activation
TCR signaling
thymocyte selection
Issue Date: 2019
Publisher: NLM (Medline)
Citation: Chen, E.W., Tay, N.Q., Brzostek, J., Gascoigne, N.R.J., Rybakin, V. (2019). A Dual Inhibitor of Cdc7/Cdk9 Potently Suppresses T Cell Activation. Frontiers in immunology 10 : 1718. ScholarBank@NUS Repository.
Rights: Attribution 4.0 International
Abstract: T cell activation is mediated by signaling pathways originating from the T cell receptor (TCR). Propagation of signals downstream of the TCR involves a cascade of numerous kinases, some of which have yet to be identified. Through a screening strategy that we have previously introduced, PHA-767491, an inhibitor of the kinases Cdc7 and Cdk9, was identified to impede TCR signaling. PHA-767491 suppressed several T cell activation phenomena, including the expression of activation markers, proliferation, and effector functions. We also observed a defect in TCR signaling pathways upon PHA-767491 treatment. Inhibition of Cdc7/Cdk9 impairs T cell responses, which could potentially be detrimental for the immune response to tumors, and also compromises the ability to resist infections. The Cdc7/Cdk9 inhibitor is a strong candidate as a cancer therapeutic, but its effect on the immune system poses a problem for clinical applications.
Source Title: Frontiers in immunology
ISSN: 16643224
DOI: 10.3389/fimmu.2019.01718
Rights: Attribution 4.0 International
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