NFkB

By Victoria Osinski

By Christina Towers, PhD

By Jamshed Arslan, Pharm. D., PhD.

The major histocompatibility complex (MHC) is responsible for binding peptide fragments arising from pathogens in order to display them on the cell surface for recognition from immune cells.  Once recognized, the foreign pathogen is typically evaded. The MHC complex is broken into two categories, MHC Class I proteins and MHC Class II proteins.  MHC complex I and II proteins are all very different and contain specific molecules to bind different peptides – in fact, they have been described as the most polymorphic genes there are.

Mammalian target of Rapamycin (mTOR) is a serine/threonine kinase that regulates cell growth, proliferation, motility and survival.

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).

Podoplanin is a mucin-type 1 transmembrane glycoprotein found in a wide range of tissues. It appears to be differentially expressed in endothelial cells of lymphatic but not blood vessel origin. In normal skin and kidney, podoplanin co-localizes with VEGFR3/FLT4, another marker for lymphatic endothelial cells. It appears to be involved in lymphangioigenesis and cell migration and is regulated by the lymphatic-specific homeobox gene Prox1. Podoplanin has also been found to be expressed on a wide variety of tumors.

COX2 is an inducible dimeric enzyme belonging to the prostaglandin G/H synthase family that enables cells to respond to growth factors, tumor promoters, and cytokines. Prostaglandins are synthesized through the creation of cyclic endoperoxides from arachidonic acid and COX2 catalyzes the committed step in the biosynthetic pathway.

Cells undergo apoptotic programmed cell death in response to various stimuli. The process is required for morphogenesis, tissue homeostasis, and host defense. Certain cytokines such as tumor necrosis factor (TNF) and Fas ligand signal through death domain-containing receptors such as tumor necrosis factor receptor 1 (TNFR1) and Fas.

RANKL is the ligand for the receptor activator of NFkB (RANK) that belongs to the tumor necrosis factor receptor (TNFR) superfamily. RANK overexpression induces the NFkB and c-Jun-terminal kinase (JNK) downstream pathways. This pathway has been studied in detail in the bone remodeling system with regards to osteoclast activity and induction.