TRAF2 suppresses basal IKK activity in resting cells and TNFalpha can activate IKK in TRAF2 and TRAF5 double knockout cells.

ABSTRACT: Tumor necrosis factor receptor (TNFR)-associated factor 2 (TRAF2) and TRAF5 are adapter proteins involved in TNFalpha-induced activation of the c-Jun N-terminal kinase and nuclear factor kappaB (NF-kappaB) pathways. Currently, TNFalpha-induced NF-kappaB activation is believed to be impaired in TRAF2 and TRAF5 double knockout (T2/5 DKO) cells. Here, we report instead that T2/5 DKO cells exhibit high basal IkappaB kinase (IKK) activity and elevated expression of NF-kappaB-dependent genes in unstimulated conditions. Although TNFalpha-induced receptor-interacting protein 1 ubiquitination is indeed impaired in T2/5 DKO cells, TNFalpha stimulation further increases IKK activity in these cells, resulting in significantly elevated expression of NF-kappaB target genes to a level higher than that in

SUBMITTER: Zhang L 

PROVIDER: S-EPMC2730456 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature