RRC ID 43895
Author Umehara H, Asai A.
Title Tributylhexadecylphosphonium bromide, a novel nuclear factor of activated T cells signaling inhibitor, blocks interleukin-2 induction associated with inhibition of p70 ribosomal protein S6 kinase phosphorylation.
Journal Biol Pharm Bull
Abstract Transcriptional factors of the nuclear factor of activated T cells (NFAT) family are involved in T cell signaling. Many NFAT signaling inhibitors, such as cyclosporin A (CsA) and tacrolimus, abrogate dephosphorylation of NFAT proteins by inhibiting calcineurin activity. In pursuit of a novel type of NFAT signaling inhibitor, we screened our chemical library using the NFAT-dependent reporter assay and identified tributylhexadecylphosphonium bromide (THPB) as a selective NFAT signaling inhibitor. THPB inhibited NFAT-dependent reporter activity, and the induction of interleukin-2 (IL-2) at both mRNA and protein levels by calcium stimulation. Moreover, THPB had an additive effect on the inhibition of IL-2 induction with CsA. Unlike CsA, THPB did not affect dephosphorylation of NFAT1, but suppressed phosphorylation of p70 ribosomal protein S6 kinase (p70S6K). These results suggest that THPB may be a novel type of NFAT signaling inhibitor that acts in association with inhibition of p70S6K phosphorylation.
Volume 35(5)
Pages 805-9
Published 2012-1-1
DOI 10.1248/bpb.35.805
PII JST.JSTAGE/bpb/35.805
PMID 22687422
MeSH Calcium / pharmacology* Cyclosporine / pharmacology* Humans Interleukin-2 / genetics Interleukin-2 / metabolism* Jurkat Cells NFATC Transcription Factors / antagonists & inhibitors* Organophosphorus Compounds / pharmacology* Phosphorylation / drug effects RNA, Messenger / metabolism Ribosomal Protein S6 Kinases, 70-kDa / antagonists & inhibitors* Signal Transduction / drug effects T-Lymphocytes / drug effects* T-Lymphocytes / metabolism
IF 1.863
Times Cited 3
Human and Animal Cells