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. 2013 Oct 16;8(10):e75483. doi: 10.1371/journal.pone.0075483

Figure 10. Model for RASSF1A regulation of NFκB and YAP.

Figure 10

RASSF1A restricts NFκB activity by interfering with the ability of membrane proximal TLR/MyD88/TRAF6/IRAK2/4 to promote downstream signaling to NFκB. This results in the interference of NFκB-dependent gene transcription and the activation of inflammatory pathways. Through regulating NFκB activity (and early increases in DNA damage), RASSF1A indirectly regulates the activity (and possibly the expression) of a PTK to tyrosine phosphorylation YAP (possibly through c-Abl or c-YES). Increased PTK activity (in the absence of Rassf1a) would drive tyrosine phosphorylation of YAP and increased pY-YAP/p73 transcriptional up-regulation of pro-apoptotic genes such as Bax. Increased levels of Bax (and other p73/pY YAP targets) results in apoptosis, intestinal inflammation, oxidative (and DNA damage) and colonic injury. Sustained levels of apoptosis will result in the pro-apoptotic cleavage of c-Abl to stabilize p53. Accumulated p53 can further promote cell death and further colonic injury and poor recovery following inflammation insults.