Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation.

Cavigelli, Martin; Dolfi, Fabrizio; Claret, François X.; Karin, Michael

doi:10.1002/j.1460-2075.1995.tb00284.x

Cited by 504 publications

(403 citation statements)

References 41 publications

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“…The c-fos promoter was activated by cotransfection of a constitutively active JNK kinase (SEK)-1 and inhibited by a dominant negative JNK kinase kinase (MEKK)-1, demonstrating a role for JNK-dependent pathways in the activation of the c-fos promoter, which corroborates the results of previous studies in other cell types. (Whitmarsh et al, 1995;Janknecht and Hunter, 1997;Cavigelli et al, 1995). JNK activity was lower in tumorigenic 1170I cells than in normal HBE cells, which is consistent with the relative levels of c-fos mRNA in these cells, supporting the possibility that JNK-dependent pathways contributed to the reduction in c-fos expression associated with malignant transformation.…”

Section: Discussionmentioning

confidence: 60%

“…The activity of the SRE in the c-fos promoter is controlled by ERK-and JNK-dependent pathways, which can either activate or suppress c-fos promoter activity (Marais et al, 1993;whitmarsh et al, 1995;Janknecht and Hunter, 1997;Cavigelli et al, 1995;Gille et al, 1995;Galvin and Shi, 1997;Zinck et al, 1993). We examined the role of these pathways in the regulation of c-fos promoter activity in normal HBE and tumorigenic 1170I cells by transiently co-transfecting fos-LUC and expression vectors containing constitutively active mutant JNK kinase (SEK)-1, MEK-1, or dominant negative mutant JNK kinase kinase (MEKK)-1 cDNAs.…”

Section: Resultsmentioning

confidence: 99%

“…Ternary complex transcriptional activity is activated by mitogen activated protein (MAP) kinases, including the p42 and p44 (extracellular signal-regulated kinase; ERK) kinases, the cJun N-terminal kinases (JNK)/SAP kinases, and the p38 kinase (Karin, 1995;Marshall, 1995). MAP kinase pathway activation phosphorylates Elk-1, leading to increased Elk-1 DNA binding, ternary complex formation, and activation of the c-fos promoter (Marais et al, 1993;Whitmarsh et al, 1995;Janknecht and Hunter, 1997;Cavigelli et al, 1995;Gille et al, 1995). Binding of the ternary complex to the SRE can stimulate or inhibit c-fos promoter activity, depending on the composition and phosphorylation state of the ternary complex (Galvin and Shi, 1997;Zinck et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

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Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

et al. 1998

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The Activator Protein-1 (AP-1) complex is a dimeric transcription factor composed of fos and jun proteins that regulates cellular growth and di erentiation. We previously demonstrated a reduction in basal AP-1 transcriptional activity associated with the malignant transformation of human bronchial epithelial (HBE) cells that was, in part, a consequence of decreased c-fos expression. In this study, we investigated the mechanisms underlying the reduction in c-fos expression associated with the malignant transformation of HBE cells. c-Fos gene transcription was lower in tumorigenic HBE cells than in normal HBE cells, and the reduction in transcription involved c-fos gene promoter elements from 7327 to +40. DNaseI footprinting and band shift analyses of motifs within this c-fos promoter region, including a cyclic AMP response element (CRE), serum response element (SRE), sis-inducible element (SIE), and a YY1 site, revealed that binding to these motifs was greater in tumorigenic HBE cells than in normal HBE cells. Site-directed mutagenesis of the CRE partially relieved the repression of c-fos promoter activity in tumorigenic HBE cells. Further, the activity of the Jun N-terminal Kinase (JNK)-dependent pathway, which was a positive regulator of the c-fos promoter, was greater in normal HBE cells than in tumorigenic HBE cells. These ®ndings demonstrate a transcriptionally-mediated suppression of c-fos gene expression associated with the malignant transformation of HBE cells. The decreased activity of the c-fos promoter in tumorigenic 1170I cells appeared to involve suppression through a CRE site and reduced activation by JNK-dependent pathways.

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Section: Discussionmentioning

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

et al. 1998

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“…For example, ERK5 induced phosphorylation of the transcription factor monocyte-specific enhancer binding factor 2c, whose activation increases c-Jun expression [60]. In relation to the phosphorylation of c-jun by JNK-1, this effect could be exerted through translocation to the nucleus [61], where JNK-1 phosphorylates c-Jun and thereby enhances its transcriptional activity [54].…”

Section: Discussionmentioning

confidence: 99%

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

et al. 2009

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MAPK phosphatase-1 (MKP-1) is a protein phosphatase that plays a crucial role in innate immunity. This phosphatase inactivates ERK1/2, which are involved in two opposite functional activities of the macrophage, namely proliferation and activation. Here we found that although macrophage proliferation and activation induce MKP-1 with different kinetics, gene expression is mediated by the proximal promoter sequences localized between À380 and À180 bp. Mutagenesis experiments of the proximal element determined that CRE/AP-1 is required for LPS-or M-CSF-induced activation of the MKP-1 gene. Moreover, the results from gel shift analysis and chromatin immunoprecipitation indicated that c-Jun and CREB bind to the CRE/AP-1 box. The distinct kinetics shown by M-CSF and LPS correlates with the induction of JNK and c-jun, as well as the requirement for Raf-1. The signal transduction pathways that activate the induction of MKP-1 correlate kinetically with induction by M-CSF and LPS.Key words: Activation . Kinases . Macrophage . Phosphatases . Proliferation IntroductionMacrophages perform critical functions during the immune response. These cells are regulators of homeostasis and play an important role in innate and acquired immunity during infection, tumor growth, and wound healing [1]. In response to needs, tissue macrophages proliferate, further differentiate to more specialized macrophagic populations, or become activated. Macrophages, like many other cells of the immune system, are produced in large excess and most undergo apoptosis [2].In the presence of M-CSF, macrophages differentiate and proliferate. However, the proliferation of these cells is blocked when they are activated by Gram-negative LPS or by . Activation causes many biochemical, morphological and functional modifications. Macrophage response to M-CSF and LPS involves the phosphorylation of the three members of the MAPK family [4].MAPK are critical components of signal transduction pathways activated by a range of stimuli and they mediate a number of physiological and pathological changes in cell function [5,6]. MAPK activation requires phosphorylation on a threonine and tyrosine residue located in the activation loop. This process is reversible even in the continued presence of activating stimuli, thereby indicating that protein phosphatases regulate MAPK [7]. Although MAPK are conserved evolutionary pathways present in eukaryotic cells, the kinetics of activation and their subcellular compartmentalization are cell type-specific, and they orchestrate differential cellular responses. For example, in neuronal cells, sustained MAPK phosphorylation of even days is required for cellular activation or differentiation, while in fibroblasts, phosphorylation of this kinase family is very short. In contrast, to Immunol. 2009. 39: 1902-1913 Cristina Casals-Casas et al. 1902 achieve proliferation, extended activation of MAPK is required in these cells [6,7]. The correct spatio-temporal regulation of MAPK signalling is crucial in determining cellular responses to g...

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“…The JNKs have recently been found to phosphorylate and activate other transcription factors like Elk1 (Cavigelli et al, 1995) or ATF2 (Gupta et al, 1995;Livingstone et al, 1995;van Dam et al, 1995). ATF2 forms homodimers but can also readily heterodimerize with other members of the ATF and Jun/Fos families (Benbrook and Jones, 1990;Hai and Curran, 1991;Lee, 1992), thus yielding factors with extended regulatory potentials.…”

Section: Introductionmentioning

confidence: 99%

Role of the ATFa/JNK2 complex in Jun activation

et al. 1999

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The ATFa proteins, which are members of the CREB/ ATF family of transcription factors, display quite versatile properties. We have previously shown that they interact with the adenovirus E1a oncoprotein, mediating part of its transcriptional activity and heterodimerize with the Jun, Fos or related transcription factors, thereby modulating their DNA-binding speci®city. In the present study, we report the sequence requirement of the N-terminal activation domain of ATFa and demonstrate the importance of speci®c threonine residues (Thr51 and Thr53) in addition to that of the metalbinding domain, in transcriptional activation processes. We also show that the N-terminal domain of ATFa which stably binds the Jun N-terminal kinase-2 (JNK2) (Bocco et al., 1996), is not a substrate for this kinase in vivo but, instead, serves as a JNK2-docking site for ATFa-associated partners like JunD, allowing them to be phosphorylated by the bound kinase.

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Induction of c-fos expression through JNK-mediated TCF/Elk-1 phosphorylation.

Cited by 504 publications

References 41 publications

Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

Suppression of c-Fos gene transcription with malignant transformation of human bronchial epithelial cells

CREB and AP‐1 activation regulates MKP‐1 induction by LPS or M‐CSF and their kinetics correlate with macrophage activation versus proliferation

Role of the ATFa/JNK2 complex in Jun activation

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