期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 105, 期 31, 页码 10883-10888出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0805186105
关键词
I kappa B kinase; NF-kappa B; hyperplasia; p100 processing; knockin
资金
- NCI NIH HHS [P01 CA092625, CA92625] Funding Source: Medline
- NIAID NIH HHS [R37 AI054636, AI057947, R01 AI057947, AI054636] Funding Source: Medline
BAFF-R-dependent activation of the alternative NF-kappa B pathway plays an essential role in mature B cell survival. Mutations leading to overexpression of NIK and deletion of the TRAF3 gene are implicated in human multiple myeloma. We show that overexpression of NIK in mouse B lymphocytes amplifies alternative NF-kappa B activation and peripheral B cell numbers in a BAFF-R-dependent manner, whereas uncoupling NIK from TRAF3-mediated control causes maximal p100 processing and dramatic hyperplasia of BAFF-R-independent B cells. NIK controls alternative NF-kappa B signaling by increasing the protein levels of its negative regulator TRAF3 in a dose-dependent fashion. This mechanism keeps NIK protein levels below detection even when they cause B cell hyperplasia, so that contributions of NIK to B cell pathologies can easily be overlooked.
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