Journal
IMMUNITY
Volume 34, Issue 2, Pages 188-200Publisher
CELL PRESS
DOI: 10.1016/j.immuni.2011.01.014
Keywords
-
Categories
Funding
- National Institutes of Health [R01 CA081065, R56 CA081065, CA077474, R01 GM083681, T32 CA009614, R01 AI083453, P01 GM071862, R01 AI52327, R01 HL073284, R01 AI079087, P01 HL44612]
- UWCCC [P30 CA14520]
- Leukemia & Lymphoma Society
Ask authors/readers for more resources
The N-terminal nuclear export sequence (NES) of inhibitor of nuclear factor kappa B (NF-kappa B) alpha (I kappa B alpha) promotes NF-kappa B export from the cell nucleus to the cytoplasm, but the physiological role of this export regulation remains unknown. Here we report the derivation and analysis of genetically targeted mice harboring a germline mutation in I kappa B alpha NES. Mature B cells in the mutant mice displayed nuclear accumulation of inactive I kappa B alpha complexes containing a NF-kappa B family member, cReI, causing their spatial separation from the cytoplasmic I kappa B kinase. This resulted in severe reductions in constitutive and canonical NF-kappa B activities, synthesis of p100 and ReIB NF-kappa B members, noncanonical NF-kappa B activity, NF-kappa B target gene induction, and proliferation and survival responses in B cells. Consequently, mice displayed defective B cell maturation, antibody production, and formation of secondary lymphoid organs and tissues. Thus, I kappa B alpha nuclear export is essential to maintain constitutive, canonical, and noncanonical NF-kappa B activation potentials in mature B cells in vivo.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available