LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins
- Zanker, D; Pang, K; Oveissi, S; Lu, C; Faou, P; Nowell, C; Mbogo, GW; Carotta, S; Quillici, C; Karupiah, G; Hibbs, M; Nutt, SL; Neeson, P; Puthalakath, H; Chen, W;
- Journal Title
- Immunology and Cell Biology
- Publication Type
- Journal Article in press
- 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. This article is protected by copyright. All rights reserved.
- WEHI Research Division(s)
- Molecular Immunology
- PubMed ID
- Publisher's Version
- Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2018-05-18 09:33:22Last Modified: 2018-06-27 09:47:31