RT info:eu-repo/semantics/article
T1 The Unfolded Protein Response and the Phosphorylations of Activating Transcription Factor 2 in the trans-Activation of il23a Promoter Produced by β-Glucans
A1 Rodríguez, Mario
A1 Domingo, Esther
A1 Alonso Martín, Sara
A1 García Frade, Luis Javier
A1 Eiros Bouza, José María
A1 Sánchez Crespo, Mariano
A1 Fernández, Nieves
K1 Proteína
K1 β-glucanos
K1 32 Ciencias Médicas
AB Current views on the control of IL-23 production focus on theregulation ofil23a, the gene encoding IL-23 p19, by NF- Bincombination with other transcription factors. C/EBP homolo-gous protein (CHOP), X2-Box-binding protein 1 (XBP1), acti-vator protein 1 (AP1), SMAD, CCAAT/enhancer-binding pro-tein (C/EBP ), and cAMP-response element-binding protein(CREB) have been involved in response to LPS, but no data areavailable regarding the mechanism triggered by the fungalmimic and -glucan-containing stimulus zymosan, which pro-duces IL-23 and to a low extent the related cytokine IL-12 p70.Zymosan induced the mobilization of CHOP from the nuclearfractions to phagocytic vesicles. Hypha-formingCandidaalsoinduced the nuclear disappearance of CHOP. Assay of tran-scription factor binding to theil23apromoter showed anincrease of Thr(P)-71–Thr(P)-69-activating transcription fac-tor 2 (ATF2) binding in response to zymosan. PKC and PKA/mitogen- and stress-activated kinase inhibitors down-regulatedThr(P)-71–ATF2 binding to theil23apromoter andil23amRNA expression. Consistent with the current concept ofcomplementary phosphorylations on N-terminal Thr-71 andThr-69 of ATF2 by ERK and p38 MAPK, MEK, and p38 MAPKinhibitors blunted Thr(P)-69–ATF2 binding. Knockdown ofatf2mRNA with siRNA correlated with inhibition ofil23amRNA, but it did not affect the expression ofil12/23bandil10mRNA. These data indicate the following: (i) zymosan decreasesnuclear proapoptotic CHOP, most likely by promoting its accu-mulation in phagocytic vesicles; (ii) zymosan-inducedil23amRNA expression is best explained through coordinated B-and ATF2-dependent transcription; and (iii)il23aexpressionrelies on complementary phosphorylation of ATF2 on Thr-69and Thr-71 dependent on PKC and MAPK activities.
PB American Society for Biochemistry and Molecular Biology
SN 0021-9258
YR 2014
FD 2014
LK http://uvadoc.uva.es/handle/10324/45314
UL http://uvadoc.uva.es/handle/10324/45314
LA eng
NO Journal of Biological Chemistry, 2014, vol. 289, n. 33, p. 22942-22957
NO Producción Científica
DS UVaDOC
RD 11-jul-2024