Table 1 Select examples of mutant p53 separation-of-function.
Function | Pro- or anti-proliferative or survival | Loss or retention of WT function | Experimental evidence | Ref |
|---|---|---|---|---|
DNA damage response | Pro | Loss | Mutants (V173M, I195S, R248Q, R273H, insG282) repress transcriptional program in Eμ-Myc lymphoma cell lines | [32] |
Antioxidant response | Pro | Retain | R248W mutant in HCT116 cells retains MDM2-ATF4 antioxidant response to survive in serine and glycine depleted conditions | [50] |
Autophagy | Pro | Retain | R175H, G245S, R248W, R249S, R273H retain the ability to suppress autophagy, which may promote genetic instability and pro-tumorigenic inflammation, among other oncogenic events | [51] |
Chromatin remodeling | Pro | Retain | R273H mutant interacts with SWI/SNF in MDA-468 cells to increase pro-angiogenic VEGFR2 expression | [52] |
Metastasis | Pro | Retain | Exon 6 truncating mutations retain the pro-metastatic capabilities of p53-psi | [20] |
Apoptosis | Anti | Retain | E180R mutant activates Puma to sensitize an NRasG12D;AML1/ETO9a AML mouse model to chemotherapy | [53] |
Cell cycle arrest | Anti | Loss | Mutants (R175H, R273H, R273H/P309S) form a complex with NF-Y to upregulate pro-proliferative genes, resulting in aberrant cell cycle progression after DNA damage | [54] |
