tBID

tBID is a truncated form of the Bcl-2 family protein BID, produced when full-length BID is proteolytically cleaved during activation of death receptor pathways. The major cleavage, by caspase-8 at a specific aspartate residue, generates tBID, a C-terminal fragment of approximately 15–17 kDa. This truncated protein is competent to relocate to mitochondria where it promotes apoptosis in response to extrinsic signals.

In the mitochondria, tBID activates the pro-apoptotic effector proteins BAX and BAK, inducing mitochondrial outer membrane permeabilization. This leads to the release of cytochrome c and other pro-apoptotic factors into the cytosol, formation of the apoptosome with Apaf-1, and activation of caspase-9, followed by downstream effector caspases such as caspase-3. Through this mechanism, tBID serves as a critical link between extrinsic death receptor signaling and the intrinsic mitochondrial pathway of apoptosis, amplifying the cell death signal.

The activity and availability of tBID are tightly regulated. Anti-apoptotic Bcl-2 family members (such as BCL-2, BCL-XL, and MCL-1) can bind and sequester tBID, preventing BAX/BAK activation. Post-translational modifications, including phosphorylation and ubiquitination, influence tBID stability and function. In cytotoxic lymphocytes, granzyme B can also cleave BID to produce tBID, enabling rapid mitochondrial amplification of the death signal.

Biological and clinical relevance includes its essential role in many Fas- or TRAIL-induced apoptotic responses, as well as its contribution to cell-type–specific sensitivity to death ligands and to mechanisms of apoptosis resistance in disease contexts.