Akt regulates basal and induced processing of NF-κB2 (p100) to p52

被引:63
作者
Gustin, Jason A.
Korgaonkar, Chandrashekhar K.
Pincheira, Roxana
Li, Qiutang
Donner, David B.
机构
[1] Univ Calif San Francisco, Dept Surg, San Francisco, CA 94143 USA
[2] Indiana Univ, Sch Med, Dept Microbiol & Immunol, Indianapolis, IN 46202 USA
[3] Indiana Univ, Sch Med, Walther Oncol Ctr, Indianapolis, IN 46202 USA
[4] Walther Canc Inst, Indianapolis, IN 46208 USA
[5] Salk Inst Biol Studies, Genet Lab, La Jolla, CA 92037 USA
关键词
D O I
10.1074/jbc.M507373200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
NF-kappa B is a family of transcription factors important for innate and adaptive immunity. NF-kappa B is restricted to the cytoplasm by inhibitory proteins that are degraded when specifically phosphorylated, permitting NF-kappa B to enter the nucleus and activate target genes. Phosphorylation of the inhibitory proteins is mediated by an I kappa B kinase (IKK) complex, which can be composed of two subunits with enzymatic activity, IKK alpha and IKK beta. The preferred substrate for IKK beta is I kappa B alpha, degradation of which liberates p65 (RelA) to enter the nucleus where it induces genes important to innate immunity. IKK alpha activates a non-canonical NF-kappa B pathway in which p100 (NF- kappa B2) is processed to p52. Once produced, p52 can enter the nucleus and induce genes important to adaptive immunity. This study shows that Akt binds to and increases the activity of IKK alpha and thereby increases p52 production in cells. Constitutively active Akt augments non-canonical NF-alpha B activity, whereas kinase dead Akt or inhibition of phosphatidylinositol 3-kinase have the opposite effect. Basal and ligand-induced p52 production is reduced in mouse embryo fibroblasts deficient in Akt1 and Akt2 compared with parental cells. These observations show that Akt plays a role in activation of basal and induced non-canonical NF-kappa B activity.
引用
收藏
页码:16473 / 16481
页数:9
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