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RAS and PD-L1: A Masters’ Liaison in Cancer Immune Evasion
Nicole Glodde, Michael Hölzel Immunity Volume 47, Issue 6, Pages (December 2017) DOI: /j.immuni Copyright © 2017 Elsevier Inc. Terms and Conditions
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Figure 1 Oncogenic RAS Signaling Impairs Tumor Immune Surveillance through Stabilization of PD-L1 mRNA Constitutively activated receptor tyrosine kinases (RTKs) or RAS mutations cause oncogenic RAS signaling in cancer cells. RAS activates the RAF-MEK-ERK downstream signaling cascade, which leads to increased ROS production and activation of the stress kinases p38 and MK2. MK2 then phosphorylates the RNA-binding protein TTP (tristetraprolin, also known as ZFP36). Phosphorylation of TTP reduces its activity to degrade PD-L1 mRNA via binding to AU-rich elements (AREs) in the 3′ UTR. As a consequence, increased PD-L1 mRNA level leads to increased PD-L1 protein expression on the surface of cancer cells and impaired anti-tumor immunity. Immunity , DOI: ( /j.immuni ) Copyright © 2017 Elsevier Inc. Terms and Conditions
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