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Dual proteolytic pathways govern glycolysis and immune competence.

Lu, Wei and Zhang, Yu and McDonald, David O and Jing, Huie and Carroll, Bernadette and Robertson, Nic and Zhang, Qian and Griffin, Helen and Sanderson, Sharon and Lakey, Jeremy H and Morgan, Neil V and Reynard, Louise N and Zheng, Lixin and Murdock, Heardley M and Turvey, Stuart E and Hackett, Scott J and Prestidge, Tim and Hall, Julie M and Cant, Andrew J and Matthews, Helen F and Koref, Mauro F Santibanez and Simon, Anna Katharina and Korolchuk, Viktor I and Lenardo, Michael J and Hambleton, Sophie and Su, Helen C (2014) Dual proteolytic pathways govern glycolysis and immune competence. Cell, 159 (7). pp. 1578-90. ISSN 1097-4172. This article is accessible to all HEFT staff and students via NICE journals and databases http://www.nice.org.uk/about/what-we-do/evidence-services/journals-and-databases by using their HEFT Athens login IDs

Full text not available from this repository.
Official URL: http://www.cell.com/cell/fulltext/S0092-8674(14)01...

Abstract

Proteasomes and lysosomes constitute the major cellular systems that catabolize proteins to recycle free amino acids for energy and new protein synthesis. Tripeptidyl peptidase II (TPPII) is a large cytosolic proteolytic complex that functions in tandem with the proteasome-ubiquitin protein degradation pathway. We found that autosomal recessive TPP2 mutations cause recurrent infections, autoimmunity, and neurodevelopmental delay in humans. We show that a major function of TPPII in mammalian cells is to maintain amino acid levels and that TPPII-deficient cells compensate by increasing lysosome number and proteolytic activity. However, the overabundant lysosomes derange cellular metabolism by consuming the key glycolytic enzyme hexokinase-2 through chaperone-mediated autophagy. This reduces glycolysis and impairs the production of effector cytokines, including IFN-γ and IL-1β. Thus, TPPII controls the balance between intracellular amino acid availability, lysosome number, and glycolysis, which is vital for adaptive and innate immunity and neurodevelopmental health.

Item Type: Article
Additional Information: This article is accessible to all HEFT staff and students via NICE journals and databases http://www.nice.org.uk/about/what-we-do/evidence-services/journals-and-databases by using their HEFT Athens login IDs
Subjects: WS Paediatrics. Child health
Divisions: Womens and Childrens > Paediatrics
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Depositing User: Mrs Caroline Tranter
Date Deposited: 31 May 2015 07:25
Last Modified: 31 May 2015 07:25
URI: http://www.repository.heartofengland.nhs.uk/id/eprint/945

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