The short version here;
http://circres.ahajournals.org/content/112/12/1526.extract.html?etoc
Hypoxia–reoxygenation can induce inflammation by activating
nuclear factor (NF)-κB. In endothelial cells, this process is
critical for the pathogenesis of many chronic
inflammatory conditions, such as atherosclerosis and autoimmune disease.
Recent
publication from Evans’s laboratory shows the
critical role of deubiquitinating enzyme Cezanne, regulating its extent
of NF-κB
activation and expression of inflammatory genes.1
In particular, they showed that the inhibition of polyubiquitination of
TNF receptor associated factor (TRAF) 6 is a specific
anti-inflammatory mechanism by Cezanne. In this
editorial, we briefly review the TRAF6-mediated NF-κB signaling and
other
posttranslational modifications that play a key
role in modulating endothelial cell inflammation.
Article, see p 1583
NF-κB transcription factor complexes consist of a heterodimer of p65 (RelA) and p50 or p52.2
In most nonstimulated cells, p65-containing NF-κB complexes are kept in
an inactive cytoplasmic form, bound to one family
of inhibitor proteins, the inhibitory κBs
(IκBs). Two IκB kinases, IKKα and IKKβ, target phosphorylation of IκB
after hypoxia–reoxygenation,
cytokine, or ultraviolet stress stimulation.
Phosphorylation of IκBs promotes their ubiquitination and degradation by
the
proteasome, which releases the p65 complex,
allowing it to translocate to the nucleus.3
An ubiquitin E2 conjugating enzyme of the ubiquitin-conjugating enzyme
(Ubc)4/5 family and the SCF-βTrCP E3 ligase (Skp1-Cul1-F-box
ligase containing the F-box beta protein βTrCP)
execute ubiquitination of IκB. Once IκB is phosphorylated, p-transducin
repeat
containing protein 1 (βTrCP1) and βTrCP2
associate with phosphorylated IκB.4,5 The polyubiquitinated IκB is selectively degraded by the 26S proteasome, and then mature p52 and Full story here;
http://circres.ahajournals.org/content/112/12/1526.full
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