IkappaB kinase epsilon interacts with p52 and promotes transactivation via p65.
The members of the NF-kappaB transcription factor family are key regulators of gene expression in the immune response. Different combinations of NF-kappaB subunits not only diverge in timing to induce transcription but also recognize varying sequences of the NF-kappaB-binding site of their target genes. The p52 subunit is generated as a result of processing of NF-kappaB2 p100. Here, we demonstrate that the non-canonical IkappaB kinase epsilon (IKKepsilon) directly interacts with p100. In a transactivation assay, IKKepsilon promoted the ability of p52 to transactivate gene expression. This effect was indirect, requiring p65, which was shown to be part of the IKKepsilon-p52 complex and to be phosphorylated by IKKepsilon. These novel interactions reveal a hitherto unknown function of IKKepsilon in the regulation of the alternative NF-kappaB activation pathway involving p52 and p65.
Wietek
Claudia
C
School of Biochemistry and Immunology, Trinity College, Dublin 2, Ireland. wietekc@gmail.com
Cleaver
Catherine S
CS
Ludbrook
Valerie
V
Wilde
Jonathan
J
White
Julia
J
Bell
David J
DJ
Lee
Michael
M
Dickson
Marion
M
Ray
Keith P
KP
O'Neill
Luke A J
LA
D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D006801:Humans; D051550:I-kappa B Kinase / Q000378:metabolism*; D051379:Mice; D052003:NF-kappa B p52 Subunit / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D015533:Transcriptional Activation / Q000502:physiology*
D052003:NF-kappa B p52 Subunit; D051996:Transcription Factor RelA; D051550:I-kappa B Kinase