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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.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 |
| Related URLs: | |
| 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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