B-cell lymphoma 3-encoded protein (BCL3) (BCL3)

B-cell lymphoma 3-encoded protein (BCL3) is a unique member of the IκB (inhibitor of kappa B) family that functions primarily as a transcriptional co-activator in the nucleus (UniProt P20264). Unlike typical IκB proteins that sequester NF-kappaB in the cytoplasm, BCL3 interacts with nuclear NF-kappaB p50 or p52 homodimers to facilitate the transcription of genes involved in cell survival, proliferation, and the immune response (PubMed: 24513241). Originally identified through its involvement in the t(14;19) chromosomal translocation in B-cell chronic lymphocytic leukemia, BCL3 is now recognized as a proto-oncogene overexpressed in various solid tumors, including breast, lung, and colorectal cancers (PubMed: 30104630). In these contexts, it promotes tumor progression, metastasis, and resistance to apoptosis. Because it acts as a critical node in oncogenic signaling, BCL3 is an emerging therapeutic target for oncology. Current drug discovery efforts focus on small molecule inhibitors, such as UC-I13, which disrupt the BCL3-NF-kappaB interaction, and PROTAC-based strategies designed to induce targeted degradation of the BCL3 protein (PubMed: 28655774).

Other names

BCL-3B-cell CLL/lymphoma 3Proto-oncogene BCL3

Inhibition of the interaction between BCL3 and NF-kappaB p50 or p52 homodimers to prevent the transcriptional activation of pro-survival and pro-proliferative genes (PubMed: 28655774).