Stimulus induced phosphorylation of IKKβ followed by protein kinase-A-mediated phosphorylation of IκBα and rapid release and import of p65:p50 dimers. Postinduction, the newly synthesized IκBα not only sequesters DNA bound p65 but also shuttles to the cytoplasm to quench the free p50:p65 dimers.

CK1γ1 phosphorylation of p65 at S536 promotes p65 degradation by an E3 ligase complex composed of Cullin2 and COMMD1 to inhibit RIG-I/TLR signalling [91]. An important part of NF-κB regulation is the negative feedback loop that is created …

NF-κB家族由P50、P52、P65、c-Rel和RelB五个成员组成。它们分别由NFKB1, NFKB2, RELA, REL和RELB基因进行编码。 每个成员都有一个N端Rel同源结构域（RHD），负责其与DNA结合以及二聚化。 在P65、c-Rel和RelB中，存在着转录激活区域——TAD，对基因表达起正向调节的作用。 P50和P52不存在转录激活区域，它们的同型二聚体可以抑制转录。 二、IκB蛋白家族. IκB蛋白家族包括八个成员：IκBα、IκBβ、IκBγ、 IκBζ (zeta) 、IκBε、Bcl-3、p100和p105 。 主要 …

I κ B degradation reveals a nuclear localization sequence on NF- κ B proteins (e.g., a p50-p65 heterodimer) allowing them to migrate to the nucleus, bind to specific κ B-sites and regulate target gene transcription.

For example, deacetylation of p65 by HDAC3 promotes its binding to nuclear IkBa to result in an IkBa-dependent nuclear export of the p65–IkBa complex [17]. Thus, IkB has both cytoplasmic and nuclear roles in regulating the NF-kB pathway.

Jan 1, 2005 · Activation of NF-κB mainly occurs via IκB kinase (IKK)-mediated phosphorylation of inhibitory molecules, including IκBα. Optimal induction of NF-κB target genes also requires phosphorylation of NF-κB proteins, such as p65, within their transactivation domain by a variety of kinases in response to distinct stimuli.

Oct 14, 2005 · The association of the NF-kappaB p65/p50 dimer with IkappaBalpha plays a pivotal role in regulating its nuclear translocation and gene transcription. In addition, serine phosphorylation at various sites of the p65 subunit has been …

Overexpression of p65 increases endogenous IKB protein in both carcinoma and lymphoid cells by two mechanisms: protein stabilization and increased transcription of IKB mRNA. In contrast, p65zX, a naturally occurring splice variant, fails o markedly augment IKB protein levels.

Oct 30, 2018 · Hence, the NF-κB p65 signaling pathway has been a pivotal point for intense drug discovery and development. This review begins with an overview of p65-mediated signaling followed by discussion of strategies that directly target NF-κB …

We have examined the possibility that IKK can phosphorylate the p65 NF-κB subunit as well as IκB in the cytokine-induced NF-κB activation. In the cytoplasm of HeLa cells, the p65 subunit was rapidly phosphorylated in response to TNF-α in a time dependent manner similar to IκB phosphorylation.