+1 877 302 8632
+1 888 205 9894 (Toll-free)

NF-kappaB Signaling

NF-kappaB (核因子活化B细胞轻链增强子)是一种同源或异源二聚体转录因子,在各种信号转导通路网络中处于中枢地位。诸如细胞因子、生长因子以及激素、感染、氧化应激、某些药物和化学物质等众多信号均被传输至NF-kappaB复合物,随后继续传递,从而影响从细胞存活、凋亡、增殖到免疫应答和炎症等多个过程。此外,与其他信号通路发生的串扰也比较严重,如MAPK信号和p53通路 。因此,它们极具多效性,即会影响大量表型性状 。

NF-kappaB是一种存在于哺乳动物中的同源或异二聚体复合物,由RelA/p65、RelB、c-Rel、NFKB1/p105/p50和NFKB2/p100/p52等含Rel同源结构域(RHD)的蛋白构成。经典通路的异源二聚体RELA/p50复合物是其中含量最丰富的部分。所有NF-kB蛋白均具有N末端RHD,后者作为二聚化介质可以使前者结合至IkappaB抑制子,在DNA结合中发挥着必不可少的作用。然而,NF-kappaB蛋白却可以通过其C末端进行区分:RELA、RELB和c-Rel 包含的I类蛋白的特征在于其反式激活结构域,而 II类蛋白NFKB1/p105/p50和NFKB2/p100/p52则具有锚蛋白重复转录抑制结构域 。 在经典通路中,通过与抑制IkappaB蛋白的相互作用,NF-kappaB在细胞质中处于非激活状态。在上述任一刺激引发的NF-kappaB信号传导刺激下,这些调节因子被由蛋白激酶IKKalpha、IKKbeta和NEMO构成的IKK激酶复合物 磷酸化。磷酸化为蛋白酶体降解标志IkappaB抑制子,从而将NF-kappaB转为游离状态。一旦转入游离状态,NF-kB将被翻译后的修饰进一步活化并转运至它与特异kappaB元素交互作用的细胞核内 。

根据细胞类型和接收到的刺激性质,非经典通路 也可以使用。该通路的核心调节子为NF-kappaB诱导激酶(NIK),它可以激活IKKalpha,从而导致P100的磷酸化。p100然后被处理为p52蛋白,由此促使p52/RelB NF-kappaB 二聚体发生激活和核移位,并诱导靶向基因的表达。 经典通路并不依赖蛋白质合成,并且会对众多刺激迅速作出响应,从而促成各种各样的下游效应。与此相反,非经典通路则较为缓慢和持久,且只会对信号的某一子集作出响应,从而产生某些更具特异性的效应。








MYD88 (Myeloid Differentiation Primary Response Gene (88)):

This gene encodes a cytosolic adapter protein that plays a central role in the innate and adaptive immune response. This protein functions as an essential signal transducer in the interleukin-1 and Toll-like receptor signaling pathways. These pathways regulate that activation of numerous proinflammatory genes. The encoded protein consists of an N-terminal death domain and a C-terminal...   更多...

TRADD (TNFRSF1A-Associated Via Death Domain):

The protein encoded by this gene is a death domain containing adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein binds adaptor protein TRAF2, reduces the recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2, and thus suppresses TRAF2 mediated apoptosis. This protein can also interact with receptor...   更多...

KHDRBS1 (KH Domain Containing, RNA Binding, Signal Transduction Associated 1):

SLC39A3 (Solute Carrier Family 39 (Zinc Transporter), Member 3):


IL1A (Interleukin 1 alpha):

The protein encoded by this gene is a member of the interleukin 1 cytokine family. This cytokine is a pleiotropic cytokine involved in various immune responses, inflammatory processes, and hematopoiesis. This cytokine is produced by monocytes and macrophages as a proprotein, which is proteolytically processed and released in response to cell injury, and thus induces apoptosis. This gene and...   更多...

TNF - Tumor Necrosis Factor

This gene encodes a multifunctional proinflammatory cytokine that belongs to the tumor necrosis factor (TNF) superfamily. This cytokine is mainly secreted by macrophages. It can bind to, and thus functions through its receptors TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR. This cytokine is involved in the regulation of a wide spectrum of biological processes including cell proliferation, differentiation,...   更多...


TRAF1 (TNF Receptor-Associated Factor 1):

The protein encoded by this gene is a member of the TNF receptor (TNFR) associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from various receptors of the TNFR superfamily. This protein and TRAF2 form a heterodimeric complex, which is required for TNF-alpha-mediated activation of MAPK8/JNK and NF-kappaB. The protein complex formed by this...   更多...

TRAF2 (TNF Receptor-Associated Factor 2):

The protein encoded by this gene is a member of the TNF receptor associated factor (TRAF) protein family. TRAF proteins associate with, and mediate the signal transduction from members of the TNF receptor superfamily. This protein directly interacts with TNF receptors, and forms a heterodimeric complex with TRAF1. This protein is required for TNF-alpha-mediated activation of MAPK8/JNK and...   更多...

Growth factors

EGF (Epidermal Growth Factor):

This gene encodes a member of the epidermal growth factor superfamily. The encoded protein is synthesized as a large precursor molecule that is proteolytically cleaved to generate the 53-amino acid epidermal growth factor peptide. This protein acts a potent mitogenic factor that plays an important role in the growth, proliferation and differentiation of numerous cell types. This protein acts by...   更多...

NGFB (Nerve Growth Factor beta):

This gene is a member of the NGF-beta family and encodes a secreted protein which homodimerizes and is incorporated into a larger complex. This protein has nerve growth stimulating activity and the complex is involved in the regulation of growth and the differentiation of sympathetic and certain sensory neurons. Mutations in this gene have been associated with hereditary sensory and autonomic...   更多...


BCL3 (B-Cell CLL/lymphoma 3):

This gene is a proto-oncogene candidate. It is identified by its translocation into the immunoglobulin alpha-locus in some cases of B-cell leukemia. The protein encoded by this gene contains seven ankyrin repeats, which are most closely related to those found in I kappa B proteins. This protein functions as a transcriptional co-activator that activates through its association with NF-kappa B...   更多...

NFKBIA (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, alpha):

This gene encodes a member of the NF-kappa-B inhibitor family, which contain multiple ankrin repeat domains. The encoded protein interacts with REL dimers to inhibit NF-kappa-B/REL complexes which are involved in inflammatory responses. The encoded protein moves between the cytoplasm and the nucleus via a nuclear localization signal and CRM1-mediated nuclear export. Mutations in this gene have...   更多...

NFKBIB (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, beta):

NFKBIE (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, epsilon):

NFKBIZ (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells Inhibitor, zeta):


IRAK1 (Interleukin-1 Receptor-Associated Kinase 1):

This gene encodes the interleukin-1 receptor-associated kinase 1, one of two putative serine/threonine kinases that become associated with the interleukin-1 receptor (IL1R) upon stimulation. This gene is partially responsible for IL1-induced upregulation of the transcription factor NF-kappa B. Alternatively spliced transcript variants encoding different isoforms have been found for this gene....   更多...

RIPK1 (Receptor (TNFRSF)-Interacting serine-threonine Kinase 1):

Serine-threonine kinase which transduces inflammatory and cell-death signals (necroptosis) following death receptors ligation, activation of pathogen recognition receptors (PRRs), and DNA damage. Upon activation of TNFR1 by the TNF-alpha family cytokines, TRADD and TRAF2 are recruited to the receptor. Ubiquitination by TRAF2 via 'Lys-63'-link chains acts as a critical enhancer of communication...   更多...

Protein kinases

CHUK (conserved Helix-Loop-Helix Ubiquitous Kinase):

This gene encodes a member of the serine/threonine protein kinase family. The encoded protein, a component of a cytokine-activated protein complex that is an inhibitor of the essential transcription factor NF-kappa-B complex, phosphorylates sites that trigger the degradation of the inhibitor via the ubiquination pathway, thereby activating the transcription factor. [provided by RefSeq, Jul 2008].   更多...

IKBKG (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase gamma):

This gene encodes the regulatory subunit of the inhibitor of kappaB kinase (IKK) complex, which activates NF-kappaB resulting in activation of genes involved in inflammation, immunity, cell survival, and other pathways. Mutations in this gene result in incontinentia pigmenti, hypohidrotic ectodermal dysplasia, and several other types of immunodeficiencies. Multiple transcript variants encoding...   更多...

IKBKB (Inhibitor of kappa Light Polypeptide Gene Enhancer in B-Cells, Kinase beta):

MAP3K14 (Mitogen-Activated Protein Kinase Kinase Kinase 14):


EGFR (Epidermal Growth Factor Receptor):

The protein encoded by this gene is a transmembrane glycoprotein that is a member of the protein kinase superfamily. This protein is a receptor for members of the epidermal growth factor family. EGFR is a cell surface protein that binds to epidermal growth factor. Binding of the protein to a ligand induces receptor dimerization and tyrosine autophosphorylation and leads to cell proliferation....   更多...

IL1R1 (Interleukin 1 Receptor, Type I):

The protein encoded by this gene is a cytokine receptor that belongs to the interleukin 1 receptor family. This protein is a receptor for interleukin alpha (IL1A), interleukin beta (IL1B), and interleukin 1 receptor, type I(IL1R1/IL1RA). It is an important mediator involved in many cytokine induced immune and inflammatory responses. This gene along with interleukin 1 receptor, type II (IL1R2),...   更多...

TNFRSF1A (Tumor Necrosis Factor Receptor Superfamily, Member 1A):

The protein encoded by this gene is a member of the TNF-receptor superfamily. This protein is one of the major receptors for the tumor necrosis factor-alpha. This receptor can activate NF-kappaB, mediate apoptosis, and function as a regulator of inflammation. Antiapoptotic protein BCL2-associated athanogene 4 (BAG4/SODD) and adaptor proteins TRADD and TRAF2 have been shown to interact with this...   更多...

LTBR (Lymphotoxin beta Receptor (TNFR Superfamily, Member 3)):

TNFRSF11A (Tumor Necrosis Factor Receptor Superfamily, Member 11a, NFKB Activator):

Transcription factors

NFKB1 (Nuclear Factor of kappa Light Polypeptide Gene Enhancer in B-Cells 1):

This gene encodes a 105 kD protein which can undergo cotranslational processing by the 26S proteasome to produce a 50 kD protein. The 105 kD protein is a Rel protein-specific transcription inhibitor and the 50 kD protein is a DNA binding subunit of the NF-kappa-B (NFKB) protein complex. NFKB is a transcription regulator that is activated by various intra- and extra-cellular stimuli such as...   更多...

RELB (V-Rel Reticuloendotheliosis Viral Oncogene Homolog B):

NF-kappa-B is a pleiotropic transcription factor which is present in almost all cell types and is involved in many biological processed such as inflammation, immunity, differentiation, cell growth, tumorigenesis and apoptosis. NF- kappa-B is a homo- or heterodimeric complex formed by the Rel-like domain-containing proteins RELA/p65, RELB, NFKB1/p105, NFKB1/p50, REL and NFKB2/p52. The dimers...   更多...
You are here:
help 客服