Figure 6
From: CITED2 affects leukemic cell survival by interfering with p53 activation
Knockdown of CITED2 interferes with AKT-signaling on multiple levels Reduction of CITED2 levels affects multiple factors involved in regulating AKT-signaling: (1) Knockdown of CITED2 leads to reduced expression of the transcription factor SOX4 that stimulates PI3K/AKT signaling. (2) CITED2-low cells show a higher expression of the Thioredoxin-interacting protein (TXNIP) that reactivates oxidized PTEN and thereby opposes AKT downstream signaling. (3) Knockdown of CITED2 results in decreased interaction between p53 and its inhibitor MDM2, leading to increased amounts of p53 protein. (4) Reduction of CITED2 leads to increased expression of the p53 target gene PHLDA3 that competes with AKT for the binding of membrane lipids. Decreased AKT signaling results in decreased expression of the pro-survival gene BCL2 and increased apoptosis
