BCL2L11

BCL2L11, also known as BIM, is a pro-apoptotic member of the BCL-2 protein family. It encodes the BH3-only protein BIM, which promotes programmed cell death in response to cellular stress by binding and antagonizing anti-apoptotic BCL-2 family members (such as BCL-2, BCL-XL, and MCL1) and by facilitating activation of Bax and Bak. This leads to mitochondrial outer membrane permeabilization and caspase activation, culminating in apoptosis.

BIM exists in multiple isoforms produced by alternative splicing, including BIMEL, BIML, and BIMS. These isoforms share the BH3 domain but differ in their C-terminal regions, which influences subcellular localization and apoptotic potency. BIM’s activity is tightly regulated at transcriptional and post-translational levels. Transcriptionally, BIM can be upregulated by stress-responsive transcription factors such as FOXO3a under growth factor withdrawal. Post-translationally, BIM is regulated by phosphorylation: stress-activated kinases (e.g., JNK) can stabilize BIM and promote apoptosis, whereas ERK-mediated phosphorylation commonly targets BIM for proteasomal degradation, reducing its pro-apoptotic function.

Function and role in biology: BIM is essential for development and immune system homeostasis. In mice, BIM contributes to thymic negative selection and the peripheral deletion of mature lymphocytes, helping to prevent autoimmunity. BIM also participates in activation-induced cell death of T and B cells and in responses to various anticancer therapies. Altered BIM expression or splicing has been linked to resistance to targeted therapies in cancer, and a BIM deletion polymorphism has been associated with reduced apoptotic response to certain tyrosine kinase inhibitors in some patients.

Interactions: BIM exerts its effects chiefly through interactions with other BCL-2 family proteins, binding anti-apoptotic members via its BH3 domain, and, in some contexts, directly promoting Bax/Bak activation.