IKK phosphorylates RelB to promote fibroblast migration

Ebola virus disease is spreading through Guinea, Liberia. And even in USA, there is one case reported last day. Here, together with many scientists in different countries, we sequenced 99 Ebola virus genomes from 78 patients in Sierra Leone and look forward to figure out the virus origin and transmission.

Ebola virus disease (EVD) has an average case fatality rate of 78%. During the outbreak this year, the first EVD patients is in Sierra Leone, and the following patients are all believed to have attended the funeral of an EVD case from Guinea. We compared nearly 100 samples, according to the sequence similarity to draw a relationship map.

Phylogenetic comparison to all 20 genomes from earlier outbreaks suggests that the 2014 West African virus likely spread from central Africa within the past decade.

As in every Evd outbreak, the 2014 EBOV variant carries a number of genetic changes distinct to this lineage; our data do not address whether these differences are related to the severity of the outbreak.

The Ebola virus has exhibited sustained human-to-human transmission subsequently, with no evidence of additional zoonotic sources.

Unfortunately, five co-authors, who contributed greatly to public health and research efforts in Sierra Leone got the EVD and had gone before this paper published.

It is our hope that this work will aid the multidisciplinary international efforts to understand and contain this expanding epidemic.

Tnf?is a potent cytokine that plays a critical role in numerous cellular processes; particularly immune and inflammatory responses, programmed cell death, and cell migration. TNF?-induced cellular responses are a pivotal problem. NF-?B is essential for the control of immune and inflammatory responses as well as cell proliferation, apoptosis, and migration. Here, we identified the two kinases I?B kinase? (IKK?) and I?B kinase? (IKK?) as RelB interacting partners whose activation by TNF? promotes RelB phosphorylation at serine 472.

Firstly, TNF? treatment (at least 6 h) induces RelB nuclear accumulation in these cells. Nuclear RelB dissociates from its interaction with the inhibitory protein I?B? and binds to the promoter of critical migration associated genes, such as the matrix metallopeptidase 3 (MMP3).

Next, we take the advantage of the very high affinity of avidin/streptavidin for biotinylated templates and efficient single-step purification, and identified all three subunits of the IKK complex as RelB-interacting partner candidates in fibroblasts.

Finally, The GST–RelB FL protein was significantly phosphorylated by IKK in its C-terminal half. RelB serine 472 phosphorylation status controls TNF?-induced fibroblast migration.

To summary, we established RelB and its phosphorylation on serine 472 by IKK as an important positive regulatory mechanism of TNF?-induced fibroblast migration.