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Figure 6 | Molecular Cancer

Figure 6

From: Thymoquinone-induced conformational changes of PAK1 interrupt prosurvival MEK-ERK signaling in colorectal cancer

Figure 6

TQ induces changes in the PAK1-ERK1/2 complex conformation inhibiting the prosurvival role of PAK1. A. Without TQ, in cancer cells, ERK2 phosphorylates pPAK1Thr212 (I). While an interaction between pPAK1Thr212 and pPAK1Thr423 is so far not reported (II), pPAK1Thr423 is known to induce the catalytic activity of PAK1 (III) thus leading to the activation of the prosurvival ERK1/2 pathway (IV). B. Upon TQ we observed massive conformational changes of PAK1 disrupting its scaffold function in prosurvival PAK1/MEK/ERK1/2 signaling and leading to the following modified signaling: ERK1/2-PAK1 binding is reinforced preventing pPAK1Thr212 phosphorylation by ERK1/2 (I). This leads to an increased phosphorylation at the Thr423 site (II) which impairs the interference with the catalytic domain of PAK1 and prevents PAK1 activation (III) finally resulting in apoptosis induction (IV).

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