BAFF诱导成熟B细胞中NF-κB2的不依赖NEMO的加工过程。

BAFF-induced NEMO-independent processing of NF-kappa B2 in maturing B cells.

作者信息

Claudio Estefania, Brown Keith, Park Sun, Wang Hongshan, Siebenlist Ulrich

机构信息

Laboratory of Immunoregulation, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-1876, USA.

出版信息

Nat Immunol. 2002 Oct;3(10):958-65. doi: 10.1038/ni842. Epub 2002 Sep 23.

DOI:10.1038/ni842

PMID:12352969

Abstract

NF-kappa B is usually activated by signal-induced, ubiquitin-mediated degradation of its inhibitor, I kappa B. This process is initiated by phosphorylation of I kappa B by the I kappa B kinase (IKK) complex, predominantly by the IKK beta catalytic subunit, and requires the regulatory subunit IKK gamma (NEMO). Another activation pathway, with no known physiological inducers, involves ubiquitin-mediated processing of the NF-kappa B2 inhibitory protein p100 and is dependent on phosphorylation of p100 by IKK alpha. We show here that B cell-activating factor (BAFF) activates this second pathway and that this requires the BAFF receptor (BAFF-R), the NF-kappa B-inducing kinase (NIK) and protein synthesis, but not NEMO. This NEMO-independent cascade is physiologically relevant for the survival and, hence, progression of maturing splenic B cells.

摘要

核因子-κB（NF-κB）通常通过信号诱导、泛素介导的其抑制剂IκB的降解而被激活。这个过程由IκB激酶（IKK）复合物对IκB进行磷酸化启动，主要是由IKKβ催化亚基完成，并且需要调节亚基IKKγ（NEMO）。另一条激活途径，目前尚无已知的生理诱导剂，涉及泛素介导的NF-κB2抑制蛋白p100的加工过程，并且依赖于IKKα对p100的磷酸化。我们在此表明，B细胞激活因子（BAFF）激活了这第二条途径，并且这需要BAFF受体（BAFF-R）、NF-κB诱导激酶（NIK）和蛋白质合成，但不需要NEMO。这种不依赖NEMO的级联反应在生理上与成熟脾B细胞的存活以及因此与它们的进展相关。