Fig. 5: Model. | Cell Death Discovery

Fig. 5: Model.

From: Functional cooperation between ASK1 and p21Waf1/Cip1 in the balance of cell-cycle arrest, cell death and tumorigenesis of stressed keratinocytes

Fig. 5

When exposed to environmental stress or aging cultured primary mouse keratinocytes undergo a growth arrest triggered by p21. However, under stress conditions p21 counteracts ASK1-dependent apoptosis. In contrast to wild-type keratinocytes, when exposed to stress p21-deficiency impedes the block of DNA synthesis. Thus, the most severely affected p21-deficient cells are eliminated in the course of stress by ASK1-activation. We propose that ASK1 and p21 function as a checkpoint-tumor surveillance mechanism in which ASK1 represents a mechanism for compensating loss of p21 activity. Thus, loss of the p21/ASK1 axis impairs tumor surveillance with increasing the risk of tumorigenesis.

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