the protein NF-kB

Sunday March 26, 2017

Being naturally curious necessitates spending time for more discovery. This statement holds true in the presence of the conduit and the means for gathering information. As I was curious reading about bee venom and its potential role in targeting tumors, I encountered NF-kB, which I already did encounter it long ago in my virology and immunology classes.

I needed a refresh, so I sought for papers that could help me with that.

What is NF-kB again? It is the nuclear factor kappa-light-chain-enhancer of activated B cells (that’s mouthful). It has so many roles, namely in cellular growth, immunity, and oncogenesis. It is a transcription factor that upon activation through phosphorylation by the IKK (IkB kinase) protein, it will go into nucleus and bind to specific DNA sequence.

In its inactive state, it is sequestered in the cytoplasm of a cell. It is sequestered by having its nuclear localization signals masked by a protein called IkB. Thus activation of NF-kB is resulted from the degradation of the IkB protein. How does this happen? IKK phosphorylates two serine residues on IkB protein, then the IkB undergoes ubiquitination that signals for degradation by proteasomes.

NF-kB activation pathway

Then NF-kB begins turning on genes associated with it. It could lead to an inflammatory response, cell survival response, and/or cell proliferation response. Interestingly, NF-kB turns on the expression of its own repressor, IkBa. This feedback loop controls the activity of NF-kB so that cells won’t be continuously inflamed, or worst, becoming cancerous.

Interesting papers on NF-kB here:

  1. Introduction to NF-kappaB: players, pathways, perspectives
  2. The complexity of NF-κB signaling in inflammation and cancer
  3. Noncanonical NF-κB Signaling in Health and Disease
  4. NF-κB, the first quarter-century: remarkable progress and outstanding questions