Journal article
TRAF3 deficiency promotes metabolic reprogramming in B cells
Scientific reports, Vol.6(1), pp.35349-35349
10/18/2016
DOI: 10.1038/srep35349
PMCID: PMC5082756
PMID: 27752131
Abstract
The adaptor protein TNF receptor-associated factor 3 (TRAF3) is a critical regulator of B lymphocyte survival. B cell-specific TRAF3 deficiency results in enhanced viability and is associated with development of lymphoma and multiple myeloma. We show that TRAF3 deficiency led to induction of two proteins important for glucose metabolism, Glut1 and Hexokinase 2 (HXK2). This was associated with increased glucose uptake. In the absence of TRAF3, anaerobic glycolysis and oxidative phosphorylation were increased in B cells without changes in mitochondrial mass or reactive oxygen species. Chemical inhibition of glucose metabolism or glucose deprivation substantially attenuated the enhanced survival of TRAF3-deficient B cells, with a decrease in the pro-survival protein Mcl-1. Changes in Glut1 and Mcl-1 levels, glucose uptake and B cell number in the absence of TRAF3 were all dependent upon NF-κB inducing kinase (NIK). These results indicate that TRAF3 deficiency suffices to metabolically reprogram B cells, a finding that improves our understanding of the role of TRAF3 as a tumor suppressor, and suggests potential therapeutic strategies.
Details
- Title: Subtitle
- TRAF3 deficiency promotes metabolic reprogramming in B cells
- Creators
- Nurbek Mambetsariev - Immunology Graduate Program, 357 Medical Research Center, Iowa City, IA 52242-1182, USAWai W Lin - Immunology Graduate Program, 357 Medical Research Center, Iowa City, IA 52242-1182, USAAlicia M Wallis - Immunology Graduate Program, 357 Medical Research Center, Iowa City, IA 52242-1182, USALaura L Stunz - Holden Comprehensive Cancer Center, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242, USAGail A Bishop - Internal Medicine, 200 Hawkins Drive, Iowa City, Iowa 52242, USA
- Resource Type
- Journal article
- Publication Details
- Scientific reports, Vol.6(1), pp.35349-35349
- DOI
- 10.1038/srep35349
- PMID
- 27752131
- PMCID
- PMC5082756
- NLM abbreviation
- Sci Rep
- ISSN
- 2045-2322
- eISSN
- 2045-2322
- Publisher
- England
- Grant note
- P30 ES005605 / NIEHS NIH HHS R01 AI028847 / NIAID NIH HHS T32 AI007485 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS R01 CA099997 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R56 AI028847 / NIAID NIH HHS P50 CA097274 / NCI NIH HHS
- Language
- English
- Date published
- 10/18/2016
- Academic Unit
- Microbiology and Immunology; President
- Record Identifier
- 9984001139502771
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