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LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins


Zanker, D and Pang, K and Oveissi, S and Lu, C and Faou, P and Nowell, C and Mbogo, GW and Carotta, S and Quillici, C and Karupiah, G and Hibbs, ML and Nutt, SL and Neeson, P and Puthalakath, H and Chen, W, LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins, Immunology and Cell Biology, 96, (9) pp. 981-993. ISSN 0818-9641 (2018) [Refereed Article]

Copyright Statement

Copyright 2018 Australasian Society for Immunology Inc.

DOI: doi:10.1111/imcb.12163


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.

Item Details

Item Type:Refereed Article
Keywords:MHC I, LMP immunoproteosome, lymphocyte survival, degradation of BH3-only proteins
Research Division:Biomedical and Clinical Sciences
Research Group:Immunology
Research Field:Transplantation immunology
Objective Division:Health
Objective Group:Clinical health
Objective Field:Clinical health not elsewhere classified
UTAS Author:Karupiah, G (Associate Professor Guna Karupiah)
ID Code:131551
Year Published:2018
Web of Science® Times Cited:3
Deposited By:Medicine
Deposited On:2019-03-22
Last Modified:2019-04-26

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