LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3‐only proteins. Issue 9 (3rd June 2018)

• Record Type: Journal Article
• Authors: Zanker, Damien; Pang, Kenneth; Oveissi, Sara; Lu, Chunni; Faou, Pierre; Nowell, Cameron; Mbogo, George W; Carotta, Sebastian; Quillici, Cathy; Karupiah, Guna; Hibbs, Margaret L.; Nutt, Stephen L; Neeson, Paul; Puthalakath, Hamsa; Chen, Weisan
• Is Part Of: Immunology and cell biology. Volume 96:Issue 9(2018)
• Page Start: 981
• Page End: 993
• Publication Date: 2018-06-03
• Subjects: BIM -- immunoproteasome -- LMP2 -- lymphocyte differentiation -- NFκB -- survival -- T‐cell development; Immunology -- Periodicals; Cytology -- Periodicals; 616.079
• DOI: 10.1111/imcb.12163
• Languages: English
• ISSNs: 0818-9641

Abstract

Abstract: The role of the immunoproteasome is perceived as confined to adaptive immune responses given its ability to produce peptides ideal for MHC Class‐I binding. Here, we demonstrate that the immunoproteasome subunit, LMP2, has functions beyond its immunomodulatory role. Using LMP2‐deficient mice, we demonstrate that LMP2 is crucial for lymphocyte development and survival in the periphery. Moreover, LMP2‐deficient lymphocytes show impaired degradation of key BH3‐only proteins, resulting in elevated levels of pro‐apoptotic BIM and increased cell death. Interestingly, LMP2 is the sole immunoproteasome subunit required for BIM degradation. Together, our results suggest LMP2 has important housekeeping functions and represents a viable therapeutic target for cancer. Abstract : We demonstrated that proteasomes incorporating the LMP2 subunit are required for pro‐apoptotic molecule BIM degradation. In the absence of LMP2, lymphocytes in the thymus and in the periphery have significant survival issues.