antiapoptotic

Antiapoptotic refers to substances that prevent programmed cell death. They are part of the cellular decision-making that balances cell survival and death in development, tissue homeostasis, and stress responses. They can be proteins that directly inhibit apoptosis or signaling pathways that promote survival.

In the intrinsic or mitochondrial pathway, antiapoptotic Bcl-2 family proteins such as BCL-2, BCL-XL (BCL2L1), and MCL1 prevent activation of the effector proteins BAX and BAK, blocking mitochondrial outer membrane permeabilization and the release of cytochrome c. They can also bind and sequester BH3-only pro-apoptotic proteins, preventing them from activating BAX/BAK. In the extrinsic pathway, inhibitors of apoptosis proteins (IAPs) such as XIAP and c-IAP1/2 can bind caspases and inhibit their proteolytic activity, delaying or blocking apoptosis.

Regulation is complex and context-dependent. Expression and activity are controlled by transcription factors such as p53 and NF-κB, post-translational modifications, and interactions with other signaling pathways. The balance between antiapoptotic and pro-apoptotic factors determines cell fate in response to stress, DNA damage, or oncogenic signaling.

Clinical relevance is notable. Overexpression of antiapoptotic proteins is common in cancer and can confer resistance to chemotherapy and radiotherapy. Therapeutic strategies include BH3 mimetics that inhibit BCL-2 family proteins (for example, venetoclax) and IAP antagonists in development. Conversely, reduced antiapoptotic signaling has been implicated in degenerative diseases.