NFkB and p62 Both Activate and Regulate Inflammation

Thu, 05/19/2016 - 14:54

Nuclear factor kappa-light-chain-enhancer of activated B cells (NFkB) is a protein complex that regulates DNA transcription and is a critical regulator of cell survival. NFkB has long been known as a primer of inflammation, however researchers are now finding that NFkB may also regulate over-inflammation via a novel mitophagy pathway (Minton, 2016).

NFkB proteins are structurally homologous with retroviral oncoproteins originally known as v-Rel, and are now classified together as NF-κB/Rel family proteins. These include NFkB1 p50/p105, NFkB2 p52/p100, RelA/NFkB p65, RelB and c-Rel, which can function together as dimeric transcription factors to regulate gene expression via the NFkB signaling pathway (Gilmore 2008).

nbkb p100/p50 antibody nfkb p100/p50 antibody

Immuoflorescence analysis of NFkB p105/p50 antibody clone 5D10D11 (NBP2-22178) in U251 cells.

Immunoflorescence analysis of NFkB p100/p52 antibody (NBP1-87760) in A-431 cells.

The NFkB pathway is involved in important cellular processes such as stress response, inflammation, adaptive and innate immunity. Improper transcription regulation by NFkB has been linked to cancer and autoimmune diseases. 

Latent, inactive NFkB dimers are present in the cytosol of most cells at all times. This allows NFkB to be a primary transcription factor to cellular stimuli and a key factor in the inflammasome cascade (Oeckinghaus et al., 2009). Once activated, NFkB primes the NLRP3-inflammasome for activation by inducing IL-1 beta and NLRP3 expression.

The signaling adaptor p62/SQSTM1, via NFkB activation, has been identified as a positive mediator of Ras-induced inflammation and tumorigenesis (Duran et al., 2008), making it an interesting target for cancer therapies (Zhang et al., 2016).

Interestingly, researchers are now finding that NFkB also guards against excessive inflammation via a p62/SQSTM1-mediated mitophagy process. Specifically, NFkB restricts its own inflammation-promoting activity in macrophages by promoting p62/SQSTM1-mediated removal of damaged mitochondria (Zhong et al., 2016). This may serve as a negative feedback loop to control inflammation reactions and prevent tissue damage.

Novus Biologicals offers an extensive selection of fully guaranteed NFkB related research antibodies, including:

These antibodies are being used to enhance researcher understanding of NFkB’s role in the inflammation pathway. For example, the NFkB p65 antibody (NBP1-96139) was recently used to investigate inflammatory and oxidative stress responses to vascular injury (Yang et al., 2015). In another study, the c-Rel antibody (290512) was used to study the role of the NfkB inhibitor, IκBNS, in gut inflammation and infection (Annemann et al., 2015).

Minton K. Inflammasome: Anti-inflammatory effect of mitophagy. Nat Rev Immunol. 2016 Apr;16(4):206. [PMID: 26972724]

Gilmore TD. Introduction to NF-kappaB: players, pathways, perspectives. Oncogene. 2006 Oct 30;25(51):6680-4.

Oeckinghaus A, Ghosh S. The NF-κB Family of Transcription Factors and Its Regulation. Cold Spring Harb Perspect Biol. 2009 Oct; 1(4): a000034.

Duran A, Linares JF, Galvez AS, Wikenheiser K, Flores JM, Diaz-Meco MT, Moscat J. The signaling adaptor p62 is an important NF-kappaB mediator in tumorigenesis. Cancer Cell. 2008 Apr;13(4):343-54.

Zhang J, Yang Z, Dong J. P62: An emerging oncotarget for osteolytic metastasis. J Bone Oncol. 2016 Feb 3;5(1):30-7.

Zhong Z, Umemura A, Sanchez-Lopez E, Liang S, Shalapour S, Wong J, He F, Boassa D, Perkins G, Ali SR, McGeough MD, Ellisman MH, Seki E, Gustafsson AB, Hoffman HM, Diaz-Meco MT, Moscat J, Karin M. NF-κB Restricts Inflammasome Activation via Elimination of Damaged Mitochondria. Cell. 2016 Feb 25;164(5):896-910. [PMID: 26919428]

Yang Z, Zheng B, Zhang Y, He M, Zhang XH, Ma D, Zhang RN, Wu XL, Wen JK. miR-155-dependent regulation of mammalian sterile 20-like kinase 2 (MST2) coordinates inflammation, oxidative stress and proliferation in vascular smooth muscle cells. Biochim Biophys Acta. 2015 Jul;1852(7):1477-89. [PMID: 25892184]

Annemann M, Wang Z, Plaza-Sirvent C, Glauben R, Schuster M, Ewald Sander F, Mamareli P, Kühl AA, Siegmund B, Lochner M, Schmitz I. IκBNS regulates murine Th17 differentiation during gut inflammation and infection. J Immunol. 2015 Mar 15;194(6):2888-98. [PMID: 25694610]

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