Transcriptional Induction of Mitogen-activated Protein Kinase Phosphatase 1 by Retinoids

Xu, Qihe; Konta, Tsuneo; Furusu, Akira; Nakayama, Kenji; Lucio-Cazaña, Javier; Fine, Leon G.; Kitamura, Masanori

doi:10.1074/jbc.m207095200

Cited by 61 publications

(15 citation statements)

References 59 publications

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“…We also demonstrated that ERR␣ directly regulates expression of the Dusp1 gene 5= flanking region, which contains an ERR␣-responsive site and is occupied by ERR␣ in a differentiationdependent manner. This is consistent with results from previous studies demonstrating that Dusp1 is regulated by other nuclear receptors, including glucocorticoid and retinoic acid receptors (24,71). Furthermore, a subsequent search using the Ensembl mouse regulatory build (version 4) revealed ERR␤ binding to the proximal Dusp1 promoter in embryonic stem cells within the same region we identified (8,19).…”

Section: Discussionsupporting

confidence: 80%

Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway

Murray

Huss

2011

American Journal of Physiology-Cell Physiology

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Murray J, Huss JM. Estrogen-related receptor ␣ regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway. Am J Physiol Cell Physiol 301: C630 -C645, 2011. First published May 11, 2011; doi:10.1152/ajpcell.00033.2011.-Myocyte differentiation involves complex interactions between signal transduction pathways and transcription factors. The estrogen-related receptors (ERRs) regulate energy substrate uptake, mitochondrial respiration, and biogenesis and may target structural gene programs in striated muscle. However, ERR␣'s role in regulating myocyte differentiation is not known. ERR␣ and peroxisome proliferator-activated receptor-␥ coactivator-1␣ (PGC-1␣) are coordinately upregulated with metabolic and skeletal muscle-specific genes early in myogenesis. We analyzed effects of ERR␣ overexpression and loss of function in myogenic models. In C2C12 myocytes ERR␣ overexpression accelerated differentiation, whereas XCT790 treatment delayed myogenesis and resulted in myotubes with fewer mitochondria and disorganized sarcomeres. ERR␣Ϫ/Ϫ primary myocytes showed delayed myogenesis, resulting in structurally immature myotubes with reduced sarcomeric assembly and mitochondrial function. However, sarcomeric and metabolic gene expression was unaffected or upregulated in ERR␣Ϫ/Ϫ cells. Instead, ERR␣Ϫ/Ϫ myocytes exhibited aberrant ERK activation early in myogenesis, consistent with delayed myotube formation. XCT790 treatment also increased ERK phosphorylation in C2C12, whereas ERR␣ overexpression decreased early ERK activation, consistent with the opposing effects of these treatments on differentiation. The transient induction of MAP kinase phosphatase-1 (MKP-1), which mediates ERK dephosphorylation at the onset of myogenesis, was lost in ERR␣Ϫ/Ϫ myocytes and in XCT790-treated C2C12. The ERR␣-PGC-1␣ complex activates the Dusp1 gene, which encodes MKP-1, and ERR␣ occupies the proximal 5= regulatory region during early differentiation in C2C12 myocytes. Finally, treatment of ERR␣Ϫ/Ϫ myocytes with MEK inhibitors rescued normal ERK signaling and myogenesis. Collectively, these data demonstrate that ERR␣ is required for normal skeletal myocyte differentiation via modulation of MAP kinase signaling. orphan nuclear receptors; mitogen-activated protein kinases; gene regulation; skeletal muscle THE ESTROGEN-RELATED RECEPTORS (ERRs) are a family of nuclear receptor transcription factors comprising three related isoforms, ERR␣ (NR3B1), ERR␤ (NR3B2), and ERR␥ (NR3B3), encoded by distinct genes (15). Although structurally related to the estrogen receptors, ERRs are not responsive to estradiol and have no endogenous ligand identified to date. We previously showed (22) that ERR␣ and ERR␥ overexpression increases fatty acid (FA) uptake and ␤-oxidation in primary cardiac myocytes. In cell-based analyses ERR␣ is required for induction of electron transport/oxidative phosphorylation genes and mitochondrial biogenesis in conjunction with its coactivator, peroxisome proliferator-activated receptor-␥ (PPAR␥) coactivator (PG...

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Section: Discussionsupporting

confidence: 80%

Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway

Murray

Huss

2011

American Journal of Physiology-Cell Physiology

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“…NGF increases MKP-1 protein levels through both an active transcriptional mechanism and a decrease of protein degradation. The induction of MKP-1 mRNA by NGF was rapid (within 30 min) and completely blocked by actinomycin, consistent with data reported in other experimental systems (37,43). In fact, MKP-1 is considered an early response gene (20) whose transcriptional activity is controlled via a strong block of elongation in the exon I of the gene (44).…”

Section: Ngf Induces Mitochondrial Localization Of Mkp-1 Protein-supporting

confidence: 75%

Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1

Rosini

Chiara

Bonini

et al. 2004

Journal of Biological Chemistry

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The sIgG ؉ lymphoblastoid B cell line CESS spontaneously produces a high amount of nerve growth factor (NGF) and expresses both high affinity (p140 Trk-A ) and low affinity (p75 NTR ) NGF receptors. Autocrine production of NGF maintains the survival of CESS cells through the continuous deactivation of p38 MAPK, an enzyme able to induce Bcl-2 phosphorylation and subsequent cytochrome c release and caspase activation. In this paper, we show that NGF induces transcriptional activation and synthesis of MAPK phosphatase 1 (MKP-1), a dual specificity phosphatase that dephosphorylates p38 MAPK, thus preventing Bcl-2 phosphorylation. Furthermore, NGF increases MKP-1 protein stability by preventing its degradation through the proteasome pathway. Following NGF stimulation, MKP-1 protein mainly localizes on mitochondria, suggesting an interaction with p38 MAPK in this compartment. Incubation of CESS cells with MKP-1-specific antisense oligonucleotides induces cell death, which was not prevented by exogenous NGF. By contrast, overexpression of native MKP-1, but not of its catalytically impaired form, inhibits apoptosis induced by NGF neutralization in CESS cells. Thus, the molecular mechanisms underlying the survival function of NGF in CESS B cell line predominantly consist in maintaining elevated levels of MKP-1 protein, which controls p38 MAPK activation.

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“…GM cells were maintained in minimum essential medium with 0.5% FBS for 3 days to arrest cells in G 0 /G 1 phase of the cell cycle, and the effects of phosphatases on p53-mediated arrest were assessed in the presence or absence of the phosphatase inhibitor vanadate. Of note, vanadate has recently been shown to inhibit MKP1 activity in vivo (59). As shown in Fig.…”

Section: Fig 3 Transcriptional and Translational Inhibition Of Mkp1mentioning

confidence: 81%

The Phosphatase MKP1 Is a Transcriptional Target of p53 Involved in Cell Cycle Regulation

Zhou

et al. 2003

Journal of Biological Chemistry

110

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The tumor suppressor p53 protein suppresses cell growth by inducing cell cycle arrest or apoptosis. Despite the fact that p53-dependent p21-mediated G 1 arrest induced by DNA damage is well defined, the role of p53 in the cell cycle in response to the MAKP signaling remains to be determined. Here we show that MKP1, a member of the dual specificity protein phosphatase family capable of inactivating MAPKs, is a transcriptional target of p53. MKP1 mRNA and protein levels were increased upon p53 activation in several well defined p53-regulated cell systems. p53 bound to a consensus p53 binding site located in the second intron of the MKP1 gene and transactivated MKP1 in reporter gene assays. Inhibition of phosphatase activity impaired p53-mediated G 1 arrest in arrested human glioblastoma GM cells in response to growth factor stimuli. Importantly conditional expression of MKP1 prevented arrested human cancer cells from entering into the cell cycle. Thus, these results provide a novel mechanism by which p53 controls the cell cycle in response to the MAPK signaling in the absence of DNA damage and suggest that p53 may negatively control the MAKP pathway via MKP1.

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Transcriptional Induction of Mitogen-activated Protein Kinase Phosphatase 1 by Retinoids

Abstract: All-trans-retinoic acid (t-RA) inhibits hydrogen peroxide (H

Cited by 61 publications

References 59 publications

Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway

Estrogen-related receptor α regulates skeletal myocyte differentiation via modulation of the ERK MAP kinase pathway

Nerve Growth Factor-dependent Survival of CESS B Cell Line Is Mediated by Increased Expression and Decreased Degradation of MAPK Phosphatase 1

The Phosphatase MKP1 Is a Transcriptional Target of p53 Involved in Cell Cycle Regulation

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