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Description
Bcl10/CIPER/CLAP/mE10 is a widely expressed CARD (caspase recruitment domain) containing protein shown to induce apoptosis and activate NF-kappaB. The CARD domain mediates self-oligomerization, interactions with other CARD proteins and is necessary for NF-kappaB activation, although the precise mechanism which Bcl10 regulates these processes is not fully understood. The discovery of Bcl10 came from observations of the chromosomal translocation t(p22, q32) from B cell lymphomas of the mucosa-associated lymphoid tissue (MALT). This translocation results in deregulated expression of a truncated form of Bcl10 which lacks apoptotic activity and enhances transformation. Studies from Bcl10 deficient mice demonstrate that Bcl10 is essential for the activation of NF-kappaB by T- and B-cell receptors. One third of Bcl10 deficient mice developed lethal exencephaly. Surviving mice were unaffected by various apoptotic stimuli, but were severely immunodeficient and defective in antigen receptor-induced NF-kappaB activiation. PKC or T-cell receptor signaling results in a downregulation of Bcl10 protein levels, attenuating both NF-kappaB activation and cellular proliferation and also provides a negative feedback regulation of the NF-kappaB signaling to T cell signaling.Synonyms: BCL10, CARMEN, CIPER, CLAP, c-E10, mE10