| First Author | Fang J | Year | 2018 |
| Journal | Cell Rep | Volume | 22 |
| Issue | 5 | Pages | 1250-1262 |
| PubMed ID | 29386112 | Mgi Jnum | J:270852 |
| Mgi Id | MGI:6278791 | Doi | 10.1016/j.celrep.2018.01.013 |
| Citation | Fang J, et al. (2018) TRAF6 Mediates Basal Activation of NF-kappaB Necessary for Hematopoietic Stem Cell Homeostasis. Cell Rep 22(5):1250-1262 |
| abstractText | Basal nuclear factor kappaB (NF-kappaB) activation is required for hematopoietic stem cell (HSC) homeostasis in the absence of inflammation; however, the upstream mediators of basal NF-kappaB signaling are less well understood. Here, we describe TRAF6 as an essential regulator of HSC homeostasis through basal activation of NF-kappaB. Hematopoietic-specific deletion of Traf6 resulted in impaired HSC self-renewal and fitness. Gene expression, RNA splicing, and molecular analyses of Traf6-deficient hematopoietic stem/progenitor cells (HSPCs) revealed changes in adaptive immune signaling, innate immune signaling, and NF-kappaB signaling, indicating that signaling via TRAF6 in the absence of cytokine stimulation and/or infection is required for HSC function. In addition, we established that loss of IkappaB kinase beta (IKKbeta)-mediated NF-kappaB activation is responsible for the major hematopoietic defects observed in Traf6-deficient HSPC as deletion of IKKbeta similarly resulted in impaired HSC self-renewal and fitness. Taken together, TRAF6 is required for HSC homeostasis by maintaining a minimal threshold level of IKKbeta/NF-kappaB signaling. |
