NF-κB信号通路精编版.docVIP

……………………………………………………………最新资料推荐………………………………………………… PAGE PAGE 1 NF-κB信号通路 NF-κB是属于Rel家族的转录因子，参与调节与机体免疫、炎症反应、细胞分化有关的基因转录。哺乳动物细胞中有五种NF-κB/Rel都具有Rel同源区，能形成同或异二聚体，启动不同的基因转录。静息状态下，NF-κB二聚体与抑制蛋白IκB结合成三聚体而被隐蔽于细胞质，胞外刺激可激活IκB的泛素化降解途径，而使NF–κB二聚体进入胞核，调节基因转录。 Mechanism of NF-κB action. In this figure, the NF-κB heterodimer between Rel and p50 proteins is used as an example. While in an inactivated state, NF-κB is located in the cytosol complexed with the inhibitory protein? \o IκBα IκBα. Through the intermediacy of integral membrane receptors, a variety of extracellular signals can activate the enzyme? \o IκB kinase IκB kinase?(IKK). IKK, in turn, phosphorylates the IκBα protein, which results in? \o Ubiquitination ubiquitination, dissociation of IκBα from NF-κB, and eventual degradation of IκBα by the? \o Proteosome proteosome. The activated NF-κB is then translocated into the nucleus where it binds to specific sequences of DNA called response elements (RE). The DNA/NF-κB complex then recruits other proteins such as? \o Coactivator (genetics) coactivators?and? \o RNA polymerase RNA polymerase, which transcribe downstream DNA into mRNA, which, in turn, is translated into protein, which results in a change of cell function. Schematic diagram of NF-κB protein structure. There are two structural classes of NF-κB proteins: class I (top) and class II (bottom). Both classes of proteins contain a? \o N-terminus N-terminal? \o DNA-binding domain DNA-binding domain?(DBD), which also serves as a dimerization interface to other NF-κB transcription factors and, in addition, binds to the inhibitory? \o IκBα IκBα?protein. The? \o C-terminus C-terminus?of class I proteins contains a number of? \o Ankyrin repeat ankyrin repeats?and has? \o Repressor transrepression?activity. In contrast, the C-terminus of class II proteins has a? \o Transactivation transactivation?function. NF-kB信号通路与癌症 NF-kB具有明显的抑制细胞凋亡的功能，与肿瘤的发生、生长和转移等多个过程密切相关。在人类肿瘤尤其是淋巴系统的恶性肿瘤中，常可发现NF-kB家族基因的突变。NF-kB家族与癌症相关性的第