TY - JOUR
T1 - ERK1 and ERK2 activate CCAAAT/enhancer-binding protein-β-dependent gene transcription in response to interferon-γ
AU - Hu, Junbo
AU - Roy, Sanjit K.
AU - Shapiro, Paul S.
AU - Rodig, Scott R.
AU - Reddy, Sekhar P.M.
AU - Platanias, Leonidas C.
AU - Schreiber, Robert D.
AU - Kalvakolanu, Dhananjaya V.
PY - 2001/1/5
Y1 - 2001/1/5
N2 - Interferons (IFNs) regulate the expression of a number of cellular genes by activating the JAK-STAT pathway. We have recently discovered that CCAAAT/enhancer-binding protein-β (C/EBP-β) induces gene transcription through a novel IFN response element called the γ-IFN-activated transcriptional element (Roy, S. K., Wachira, S. J., Weihua, X., Hu, J., and Kalvakolanu, D. V. (2000) J. Biol. Chem. 275, 12626-12632. Here, we describe a new IFN-γ-stimulated pathway that operates C/EBP-β-regulated gene expression independent of JAK1. We show that ERKs are activated by IFN-γ to stimulate C/EBP-β-dependent expression. Sustained ERK activation directly correlated with C/EBP-βdependent gene expression in response to IFN-γ. Mutant MKK1, its inhibitors, and mutant ERK suppressed IFN-γ stimulated gene induction through the γ-IFN-activated transcriptional element. Ras and Raf activation was not required for this process. Furthermore, Raf-1 phosphorylation negatively correlated with its activity. Interestingly, C/EBP-β-induced gene expression required STAT1, but not JAK1. A C/EBP-β mutant lacking the ERK phosphorylation site failed to promote IFN-stimulated gene expression. Thus, our data link C/EBP-β to IFN-γ signaling through ERKs.
AB - Interferons (IFNs) regulate the expression of a number of cellular genes by activating the JAK-STAT pathway. We have recently discovered that CCAAAT/enhancer-binding protein-β (C/EBP-β) induces gene transcription through a novel IFN response element called the γ-IFN-activated transcriptional element (Roy, S. K., Wachira, S. J., Weihua, X., Hu, J., and Kalvakolanu, D. V. (2000) J. Biol. Chem. 275, 12626-12632. Here, we describe a new IFN-γ-stimulated pathway that operates C/EBP-β-regulated gene expression independent of JAK1. We show that ERKs are activated by IFN-γ to stimulate C/EBP-β-dependent expression. Sustained ERK activation directly correlated with C/EBP-βdependent gene expression in response to IFN-γ. Mutant MKK1, its inhibitors, and mutant ERK suppressed IFN-γ stimulated gene induction through the γ-IFN-activated transcriptional element. Ras and Raf activation was not required for this process. Furthermore, Raf-1 phosphorylation negatively correlated with its activity. Interestingly, C/EBP-β-induced gene expression required STAT1, but not JAK1. A C/EBP-β mutant lacking the ERK phosphorylation site failed to promote IFN-stimulated gene expression. Thus, our data link C/EBP-β to IFN-γ signaling through ERKs.
UR - http://www.scopus.com/inward/record.url?scp=0035808316&partnerID=8YFLogxK
U2 - 10.1074/jbc.M004885200
DO - 10.1074/jbc.M004885200
M3 - Article
C2 - 10995751
AN - SCOPUS:0035808316
SN - 0021-9258
VL - 276
SP - 287
EP - 297
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 1
ER -