Proc Natl Acad Sci U S A 2007,
PMID: 18003900
Hayashi, Tomoko; Mo, Ji-Hun; Gong, Xing; Rossetto, Cyprian; Jang, Angela; Beck, Lucinda; Elliott, Gregory I; Kufareva, Irina; Abagyan, Ruben; Broide, David H; Lee, Jongdae; Raz, Eyal
3-Hydroxyanthranilic acid (HAA), a compound generated during tryptophan metabolism initiated by indoleamine 2,3-dioxygenase, is known to induce T cell death, but its molecular target is not known. Here we report that HAA inhibits NF-kappaB activation upon T cell antigen receptor engagement by specifically targeting PDK1. Inhibition of NF-kappaB by HAA leads to dysfunction and cell death of activated Th2 cells, which in turn suppresses experimental asthma. Inhibition of NF-kappaB and induction of apoptosis is specific to CD4 T cells because HAA does not inhibit NF-kappaB activation or induce cell death upon Toll-like receptor 4 stimulation in dendritic cells. Thus, HAA is a natural inhibitor that restrains T cell expansion and activation.
Diseases/Pathways annotated by Medline MESH: Asthma, Disease Models, Animal
Document information provided by NCBI PubMed
Text Mining Data
NF-kappaB ⊣ PDK1: "
Here we report that HAA
inhibits NF-kappaB activation upon T cell antigen receptor engagement by specifically targeting
PDK1
"
Manually curated Databases
-
IRef Biogrid Interaction:
MAPK8
—
JUN
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
PDK1
—
PDK1
(direct interaction, enzymatic study)
-
IRef Biogrid Interaction:
CHUK
—
NFKBIA
(direct interaction, enzymatic study)
-
IRef Dip Interaction:
MAPK8
—
JUN
(direct interaction, protein kinase assay)
In total, 3 gene pairs are associated to this article in curated databases