RKIP inhibits NF-kappaB in cancer cells by regulating upstream signaling components of the IkappaB kinase complex.

Abstract:

:RKIP was first identified as an inhibitor of the Raf-MEK-ERK signaling pathway. RKIP was also found to play an important role in the NF-kappaB pathway. Genetic and biochemical studies demonstrated that RKIP functioned as a scaffold protein facilitating the phosphorylation of IkappaB by upstream kinases. However, contrary to what one would expect of a scaffold protein, our results show that RKIP has an overall inhibitory effect on the NF-kappaB transcriptional activities. Since NF-kappaB target gene expression is subject to negative regulation involving the optimal induction of negative regulators, our data support a hypothesis that RKIP inhibits NF-kappaB activity via the auto-regulatory feedback loop by rapidly inducing the expression and synthesis of inhibitors of NF-kappaB activation.

journal_name

FEBS Lett

journal_title

FEBS letters

authors

Tang H,Park S,Sun SC,Trumbly R,Ren G,Tsung E,Yeung KC

doi

10.1016/j.febslet.2009.12.051

subject

Has Abstract

pub_date

2010-02-19 00:00:00

pages

662-8

issue

4

eissn

0014-5793

issn

1873-3468

pii

S0014-5793(09)01097-7

journal_volume

584

pub_type

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