These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Withaferin A inhibits NF-kappaB activation by targeting cysteine 179 in IKKβ.
    Author: Heyninck K, Lahtela-Kakkonen M, Van der Veken P, Haegeman G, Vanden Berghe W.
    Journal: Biochem Pharmacol; 2014 Oct 15; 91(4):501-9. PubMed ID: 25159986.
    Abstract:
    The transcription factor NF-κB is one of the main players involved in inflammatory responses during which NF-κB becomes rapidly activated. However to maintain homeostasis, this NF-κB activation profile is only transient. Nevertheless deregulation of NF-κB activity is often observed and can lead to chronic inflammatory diseases as well as cancer. Therefore various research projects focus on the development of therapeutics that target the NF-κB activation pathway. One such compound is Withaferin A from the Ayurvedic plant Withania somnifera. Several reports already described the NF-κB inhibiting, anti-inflammatory capacity of WA, either in vitro as well as in vivo. However the underlying molecular mechanism remains largely unknown. In this paper we demonstrate a direct interaction of WA with the IKK-complex, more specifically with IKKβ, a kinase which is indispensable for the nuclear translocation of NF-κB. Hereby WA directly inhibits IKK catalytic activity. By mutation of Cys179 in IKKβ we could demonstrate loss of interaction between IKKβ and WA indicating that WA exerts its anti-inflammatory effects by targeting the crucial Cys179 residue located in the catalytic site of IKKβ. Upon docking of WA to a IKKβ homology structure model, WA was found to fit nicely into the groove of IKKβ where it can form hydrogen bond to stabilize its interaction with Cys179.
    [Abstract] [Full Text] [Related] [New Search]