Table 2.
Molecules involved in p53-dependent cellular processes and regulation of p53 activity whose expression is upregulated in C85 cells during establishment of methotrexate-induced senescence
| Process | Molecules |
|---|---|
| p53-dependent process | |
| Apoptosis induction | APAF1, BAX, DR4, DR5, FAS, LRDD, NOXA, PERP, PIG3, PUMA, TP53INP1 |
| Angiogenesis inhibition | SERPINB5, THBS1 |
| Autophagy induction | DRAM |
| Cell cycle arrest | CDKN1A, Cyclin G, GADD45A, GADD45B, GADD45G, SFN |
| Cell survival | BCL2L1 |
| DNA repair | PCNA, RRM2B |
| Glycolysis inhibition | TIGAR |
| Senescence | PAI-1 |
| Regulation of p53 activity | BRCA1, MDM2, MDM2b, PCAF, PLAGL1 |
| Autophagy | ATG12, ATG16L1, ATG16L2, ATG4A, ATG4B, ATG4D, BECN1, MAP1LC3B |
| Apoptosis regulation and execution | BAK1, CASP7, CASP9, CASP10, CFLAR, LMNA, SPTAN1 |
The relevant molecules were inferred from the canonical p53 and apoptosis signaling pathways implemented in IPA software and in Ref. [56]. The molecules upregulated during both senescence initiation and maintenance phases are printed bold, upregulated during the initiation phase are printed with a regular font and upregulated during the maintenance phase are underlined.
APAF1 apoptotic peptidase activating factor, ATG autophagy-related gene, BAK1 BCL2-antagonist/killer 1, BAX BCL2-associated X protein, BCL2L1 BCL2-like 1 nuclear gene encoding mitochondrial protein (Bcl-xL), BECN1 beclin 1, BRCA1 breast cancer 1, DRAM damage-regulated autophagy modulator, CASP7/9/10 caspase 7/9/10, CDKN1A p21waf1/cip1, CFLAR FLAME-1 (FLIP), DR4/5 death receptor 4/5, FAS TNF receptor superfamily, member 6, GADD45A/B/G growth arrest and DNA-damage-inducible alpha/beta/gamma, LMNA lamin A/C, LRDD leucine-rich repeats and death domain containing (PIDD), MAP1LC3B microtubule-associated protein 1 light chain 3 beta, NOXA phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1), PAI-1 plasminogen activator inhibitor type 1 (SERPINE2), PCAF p300/CBP-associated factor, PCNA proliferating cell nuclear antigen, PERP TP53 apoptosis effector, PIG3 tumor protein p53 inducible protein 3 (TP53I3), PLAGL1 pleiomorphic adenoma gene-like 1 (ZAC1), PUMA p53 upregulated modulator of apoptosis (BBC3), RRM2B ribonucleotide reductase M2B, SERPINB5 serpin peptidase inhibitor (maspin), SFN stratifin (14-3-3 sigma), SPTAN1 spectrin; TP53INP1 tumor protein p53 inducible nuclear protein 1 (Teap), TIGAR TP53-inducible glycolysis and apoptosis regulator (C12ORF5), THBS1 thrombospondin 1. Corresponding microarray data are presented in Table S2