Skip to main content
. Author manuscript; available in PMC: 2016 Jul 28.
Published in final edited form as: Cancer Res. 2008 Sep 1;68(17):7100–7109. doi: 10.1158/0008-5472.CAN-07-6145

Figure 6.

Figure 6

Model for p53 and p21WAF1/CIP1 regulation by EWS-FLI1 in TC252 cells. Suppression of EWS-FLI1 results in JAG1 expression by a thus far unknown mechanism. Presumably intercellular interaction between JAG1 and constitutively expressed NOTCH3 (and possibly also NOTCH2) results in γ-secretase–mediated NOTCH cleavage. The NICD translocates to the nucleus and activates CBF/CSL-dependent HEY1 expression. This leads to posttranscriptional stabilization of p53 via a thus far undefined mechanism, and p53-dependent p21WAF1/CIP1 expression. There is evidence that HEY1 (9) and CDKN1A (46) are directly bound by EWS-FLI1. However, evidence presented in this paper indicates that activation of HEY1 and CDKN1A is dependent on stimulation of NOTCH signaling. The NOTCH pathway modulators and components ectopically expressed to establish the sequence of events in this study are indicated at the top of the figure.