Fig. 3

TP53 in HNSCC cell death. Tumour protein p53 (TP53) acts on mitochondria. MOMP inhibits BCL-2 and BCL-2L1, as antiapoptotic members, and activates BAX, BBC3 (also known as PUMA) and PMAIP1 (also known as NOXA), which are proapoptotic members of the Bcl2 family, thus triggering TP53-dependent apoptosis. P53 can also downregulate the mTOR signalling pathway to promote autophagy. TP53 induces iron death by inhibiting the expression of SLC7A11 or directly acting on diamine acetyltransferase SAT1 and mitochondrial glutaminase GLS2. TP53 inhibits iron death by inhibiting the activities of dipeptidyl peptidase 4 (DPP4) and NADPH oxidase 1 (NOX1) or inducing the expression of cyclin-dependent kinase inhibitor 1 A (CDKN1A). BAK1, BCL-2 homologous antagonist/killer 1; BBC3, BCL-2-binding component 3; CDKN1A, cyclin-dependent kinase inhibitor 1 A; CYCS, cytochrome C, somatic; GLS2, glutaminase 2; GPX4, glutathione peroxidase 4; GSH, glutathione; mTOR, mechanistic target of rapamycin kinase; PMAIP1, phorbol-12–myristate-13 acetate-induced protein 1; ROS, reactive oxygen species; SLC7A11, solute carrier family 7 member 11; SAT1, spermidine/spermine N1-acetyltransferase 1