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The Proteasome System in Infection: Impact of beta 5 and LMP7 on Composition, Maturation and Quantity of Active Proteasome Complexes

MPS-Authors
http://pubman.mpdl.mpg.de/cone/persons/resource/persons81956

Joeris,  Thorsten
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82141

Schmidt,  Nicole
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81869

Ermert,  David
Department of Cellular Microbiology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82000

Krienke,  Petra
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82197

Visekruna,  Alexander
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons81969

Kaufmann,  Stefan H. E.
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

http://pubman.mpdl.mpg.de/cone/persons/resource/persons82175

Steinhoff,  Ulrich
Department of Immunology, Max Planck Institute for Infection Biology, Max Planck Society;

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Fulltext (public)

PLoS_One_2012_7_e39827.pdf
(Publisher version), 812KB

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Citation

Joeris, T., Schmidt, N., Ermert, D., Krienke, P., Visekruna, A., Kuckelkorn, U., et al. (2012). The Proteasome System in Infection: Impact of beta 5 and LMP7 on Composition, Maturation and Quantity of Active Proteasome Complexes. PLoS ONE, 7(6): e39827. doi:10.1371/journal.pone.0039827.


Cite as: http://hdl.handle.net/11858/00-001M-0000-000E-BDBA-0
Abstract
Proteasomes are the major enzyme complexes for non-lysosomal protein degradation in eukaryotic cells. Mammals express two sets of catalytic subunits: the constitutive subunits beta 1, beta 2 and beta 5 and the immunosubunits LMP2 (beta 1i), MECL-1 (beta 2i) and LMP7 (beta 5i). The LMP7-propeptide (proLMP7) is required for optimal maturation of LMP2/MECL-1-containing precursors to mature immunoproteasomes, but can also mediate efficient integration into mixed proteasomes containing beta 1 and beta 2. In contrast, the beta 5-propeptide (pro beta 5) has been suggested to promote preferential integration into beta 1/beta 2-containing precursors, consequently favouring the formation of constitutive proteasomes. Here, we show that pro beta 5 predominantly promotes integration into LMP2/MECL-1-containing precursors in IFN gamma-stimulated, LMP7-deficient cells and infected LMP7-deficient mice. This demonstrates that pro beta 5 does not direct preferential integration into beta 1/beta 2-containing precursors, but instead promotes the formation of mixed LMP2/MECL-1/beta 5 proteasomes under inflammatory conditions. Moreover, the propeptides substantially differ in their capacity to promote proteasome maturation, with proLMP7 showing a significantly higher chaperone activity as compared to pro beta 5. Increased efficiency of proteasome maturation mediated by proLMP7 is required for optimal MHC class I cell surface expression and is equally important as the catalytic activity of immunoproteasomes. Intriguingly, induction of LMP7 by infection not only results in rapid exchange of constitutive by immunosubunits, as previously suggested, but also increases the total proteasome abundance within the infected tissue. Hence our data identify a novel LMP7-dependend mechanism to enhance the activity of the proteasome system in infection, which is based on the high chaperone activity of proLMP7 and relies on accelerated maturation of active proteasome complexes.