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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 ORCID: 0000-0001-6306-4405, Hibbs, ML, Nutt, SL, Neeson, P, Puthalakath, H and Chen, W 2018 , 'LMP2 immunoproteasome promotes lymphocyte survival by degrading apoptotic BH3-only proteins' , Immunology and Cell Biology, vol. 96, no. 9 , pp. 981-993 , doi: 10.1111/imcb.12163.

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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.

Item Type: Article
Authors/Creators: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
Keywords: MHC I, LMP immunoproteosome, lymphocyte survival, degradation of BH3-only proteins
Journal or Publication Title: Immunology and Cell Biology
Publisher: Blackwell Publishing Asia
ISSN: 0818-9641
DOI / ID Number: 10.1111/imcb.12163
Copyright Information:

Copyright 2018 Australasian Society for Immunology Inc.

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