NF-ϰB

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NF-ϰB (nuclear factor of the kappa immunoglobulin light chain in B Cells) is a protein complex that activates transcription of DNA in cells[1]. It was first discovered by Dr Ranjan Sen, which was in the lab of the Nobel laureate David Baltimore. This was done using electrophoretic mobility shift assay, where the protein bound to a kappa enhancer sequence within B cell. The NK-kb transcription factors are highly conserved as they are found in organisms from the fruit fly to humans, although are absent in yeast[2].

Structure

NF-ϰB is made up of a multigene family. There are five main proteins found that make up the mammalian NF-ϰB multigene family, which are further sub-divided into two classes: I (NF-ϰB1 and NF-ϰB2 proteins) and II (RelA, Rel B and c-Rel proteins). All of these proteins share a common Rel homology domain in the N-terminus, but the Rel proteins have a transactivation domain in their C termini[3]. Whereas, the class I proteins are first translated from their genes as large precursors are known as p105 and p100, which are processed via the ubiquitin/proteasome pathway into their mature active subunits - p50 and p52 respectively. The functional structure of the NF-ϰB transcription activator is that of a heterodimer between p50 or p52 and the Rel sub-family. There are two classes of NF-ϰB proteins. Those which fall into class I contain many ankyrin repeats at the C-terminal of the protein, this means that the C-terminal is very long in comparison to those of class II. Due to these inhibiting factors, only when proteins of the first class form dimers with class II Rel proteins can they activate transcription[4]. The class II proteins have transcription activation domains in their C-terminals, the image on this link shows the difference clearly http://www.bu.edu/nf-kb/files/2011/02/figure-1.gif. (Ibid)

Function

NF-ϰb has a role in preventing harm from environmental pressures to the cell, which can be in the form of bacterial or viral infection, oxidative stress, DNA damage or cytokine production. NF-ϰB transcription factors play a role in various cellular processes, these include apoptosis (cell death), cell growth and immune responses. In addition to this they can be prevalent in diseased states such as cancer, inflammatory and autoimmune diseases[5]. NF-ϰB increases the amount of transcription that occurs by recruiting HATs and Swi/Snf to help reconstruct the chromosome so they can reach DNA for transcription. Under normal conditions, NF-ϰB is mainly cytoplasmic but when control is lost it is found highly concentrated in the nucleus[6].

References

  1. Gilmore TD. October 2006. "Introduction to NF-kappaB: players, pathways, perspectives". Oncogene; 25(51):6680–4.
  2. Sen R, Baltimore D. August 1986. "Multiple nuclear factors interact with the immunoglobulin enhancer sequences"; Cell. 46(5):705–16.
  3. Nabel GJ, Verma IM. November 1993. "Proposed NF-kappa B/I kappa B family nomenclature". Genes and Development; 7 (11):2063.
  4. Gilmore TD. October 2006. "Introduction to NF-kappaB: players, pathways, perspectives". Oncogene; 25(51):6680–4.
  5. Perkins ND. January 2007. "Integrating cell-signalling pathways with NF-kappaB and IKK function". Nature Reviews Molecular Cell Biology; 8(1): 49–62.
  6. Gilmore TD. October 2006. "Introduction to NF-kappaB: players, pathways, perspectives". Oncogene; 25(51):6680–4.
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