Cell Cycle. 2006 Jul;5(13):1438-42. Epub 2006 Jul 1.

CIAP2 inhibits anigen receptor signaling by targeting Bcl10 for degredation.External

Hu, S., Alcivar, A., Qu, L., Tang, J., Yang, X.,
--- - Abramson Family Cancer Research Institute and Department of Cancer Biology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USA.
The cellular inhibitor of apoptosis 2 (cIAP2) is a RING-containing protein ubiquitin ligase. In a high percentage of mucosa-associated lymphoid tissue (MALT) lymphomas, cIAP2 is fused to MALT1/paracaspase as a result of the t(11;18)(q21;q21) translocation. The physiological function of cIAP2 in lymphocytes and how this function may be affected by the translocation are not well understood. We have shown that cIAP2 normally inhibits antigen receptor signaling by mediating the ubiquitination and degradation of Bcl10, a critical component for antigenic signaling to NF-kappaB. The cIAP2-MALT1 fusion protein lacks this E3 activity and is incapable of ubiquitinating Bcl10, likely causing enhanced Bcl10 expression. Furthermore, cIAP2-MALT1 and Bcl10 synergistically activate NF-kappaB. These results reveal a physiological function of cIAP2, identify Bcl10 upregulation as a unifying molecular mechanism for MALT lymphomas, and define the mechanism and effects of this upregulation in t(11;18)-positive MALT lymphomas.
PMID: 16775419External
Arrow2 In vitro interaction Arrow2 In vivo interaction Arrow2 Characterization Arrow2 Functional role Arrow2 top
In vivo interaction
Overexpression DD1 DD2 Reference
Family DD1 DD2 Method Species Region Species Region
CARD Bcl-10 Link CIAP2 Co-immunoprecipitation HEK293 Not specified Not specified Not specified Not specified 16775419
(Link: click this icon to show interactions only between the two corresponding DDs)