BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells
BAFF-induced NEMO-independent processing of NF-κB2 in maturing B cells
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DOI：
10.1038/ni842
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发表时间：
2002-10-01
影响因子：
30.5
通讯作者：
Siebenlist, U
中科院分区：
文献类型：
--
作者：
Claudio, E;Brown, K;Siebenlist, U
NF-kappaB通常通过信号诱导的、泛素介导的其抑制剂IkappaB的降解而被激活。该过程由IkappaB激酶（IKK）复合物（主要是IKK β催化亚基）磷酸化IkappaB启动，并需要调节亚基IKK γ（NEMO）。另一种激活途径，没有已知的生理诱导剂，涉及泛素介导的NF-κ B2抑制蛋白p100的加工，并依赖于IKK α对p100的磷酸化。我们在这里表明，B细胞活化因子（BAFF）激活这第二条途径，这需要BAFF受体（BAFF-R），NF-κ B诱导激酶（NIK）和蛋白质合成，但不是NEMO。这种NEMO非依赖性级联反应与成熟脾B细胞的存活和进展具有生理相关性。
NF-kappaB is usually activated by signal-induced, ubiquitin-mediated degradation of its inhibitor, IkappaB. This process is initiated by phosphorylation of IkappaB by the IkappaB kinase (IKK) complex, predominantly by the IKKbeta catalytic subunit, and requires the regulatory subunit IKKgamma (NEMO). Another activation pathway, with no known physiological inducers, involves ubiquitin-mediated processing of the NF-kappaB2 inhibitory protein p100 and is dependent on phosphorylation of p100 by IKKalpha. We show here that B cell-activating factor (BAFF) activates this second pathway and that this requires the BAFF receptor (BAFF-R), the NF-kappaB-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.