Table 2.
Anti‐apoptotic mediators
| Agent | Mechanism |
|---|---|
| Intrinsic pathway | |
| Bcl‐2 (Group I), Bcl‐xL | Controls mitochondrial permeability |
| Inhibits Bax, Bak, granzyme B, p53 | |
| Extrinsic pathway | |
| c‐FLIP | Prevents caspase‐8 binding to various death receptors |
| NF‐κB | Upregulates anti‐apoptotic mediators c‐FLIP, IAPs; accelerates growth; activates anti‐apoptotic gene regulator p65 |
| Alternate pathways | |
| IAP | Mimics Bcl‐2; inhibits caspase‐9 activity |
| Survivin | Regulates cell cycle mitosis; inhibits caspases‐3,‐7 |
| XIAP | Inhibits caspase‐3,‐7,‐9; activates NF‐κB |
| Cytokine receptors | |
| JAK, STAT | Cytokine receptor interaction induces survival gene production through activation of NF‐κB |
| MAPK | Translocates to nucleus; induces genetic production of anti‐apoptotic factors |
| PKR | Phosphorylation of the protein initiation factor 2 alpha and IκB kinase complex; delays apoptosis |
| CDKs, cyclins, | Controls cell cycle machinery |
| CDK inhibitors | |
Bcl‐2, B‐cell lymphoma 2; Bcl‐xL, Bcl‐2‐associated protein xL; Bax, Bcl‐2‐associated protein x; Bak, Bcl‐2‐associated protein k; c‐FLIP, FLICE‐like inhibitory protein; NF‐κB, nuclear factor‐κB; IκB, inhibitory‐κB; IAPs, inibitor of apoptosis proteins; XIAP, X‐linked inhibitor of apoptosis protein; JAK, Janus kinase; STAT, signal transducers and activators of transcription; MAPK, mitogen‐activated protein kinase; PKR, protein kinase R; CDK, cyclin‐dependent kinase.