Regulation of the Transcriptional Activity of c-Fos by ERK

Monje, Paula V.; Hernández‐Losa, Javier; Lyons, Ruth J.; Castellone, Maria Domenica; Gutkind, J. Silvio

doi:10.1074/jbc.c500353200

Cited by 253 publications

(181 citation statements)

References 17 publications

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“…Isomerization of proline (Pro) residues by this protein has been shown to promote dephosphorylation of various molecules by PP2A (Zhou et al, 2000;Yeh et al, 2004;Monje et al, 2005). Pin1 binds Ser/Thr-Pro motifs through its WW motif and binds to a diverse set of substrates, including Cdc25 and Tau (Zhou et al, 2000;Stukenberg and Kirschner, 2001).…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Arnold

Lilly

et al. 2007

Oncogene

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The Pim protein kinases are serine threonine protein kinases that regulate important cellular signaling pathway molecules, and enhance the ability of c-Myc to induce lymphomas. We demonstrate that a cascade of events controls the cellular levels of Pim. We find that overexpression of the protein phosphatase (PP) 2A catalytic subunit decreases the activity and protein levels of Pim-1. This effect is reversed by the application of okadaic acid, an inhibitor of PP2A, and is blocked by SV40 small T antigen that is known to disrupt B subunit binding to PP2A A and C subunits. Pim-1 can coimmunoprecipitate with the PP2A regulatory B subunit, B56b, but not B56a, c, d, e or B55a. Using short hairpin RNA targeted at B56b, we demonstrate that decreasing the level of B56b increases the half-life of Pim-1 from 0.7 to 2.8 h, and decreases the ubiquitinylation level of Pim-1. We also find that Pin1, a prolyl-isomerase, is capable of binding Pim-1 and leads to a decrease in the protein level of Pim-1. On the basis of these observations, we hypothesize that phosphorylated Pim-1 binds Pin1 allowing the interaction of PP2A through B56b. Dephosphorylation of Pim-1 then allows for ubiquitinylation and protein degradation of Pim-1.

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Section: Introductionmentioning

confidence: 99%

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Arnold

Lilly

et al. 2007

Oncogene

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“…2C), indicating that Pin1 is still functioning in FGFR2-enhanced Runx2 protein stabilization. These data suggest that the FGF2-stimulated ERK pathway and Runx2 phosphorylation are intact in the Pin1-null mice, indicating that phosphorylation occurs prior to prolyl isomerization and that the MAPK-dependent phosphorylation of the (S/T)P dipeptide is a target of Pin1 (27)(28)(29). Therefore, we examined the ability of MEK1 to increase the level of Runx2 protein, as MEK1 is known to act downstream of FGF2 and to stimulate ERK/MAPK.…”

Section: Pin1-mediated Prolyl Isomerization Is Required For Runx2mentioning

confidence: 99%

“…Pin1, as a MAPK responder, has a crucial role in the oogenesis of a fruit fly (27). In addition, Pin1 target sequences are shared by several protein kinases, such as ERK (27)(28)(29), cyclin-dependent kinase (30,31), and GSK3a (32), indicating that ERK-phosphorylated Runx2 may also be the target of Pin1-mediated conformational and functional alterations.…”

mentioning

confidence: 99%

Prolyl Isomerase Pin1-mediated Conformational Change and Subnuclear Focal Accumulation of Runx2 Are Crucial for Fibroblast Growth Factor 2 (FGF2)-induced Osteoblast Differentiation

Yoon

Cho

Kim

et al. 2014

Journal of Biological Chemistry

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Background: Genetic interaction between Runx2 and Pin1 is critical for embryonic bone formation. Results: Pin1 is a critical modifying enzyme promoting both subnuclear accumulation and protein acetylation of Runx2. Conclusion: Pin1 determines the fate of Runx2 protein in osteoblast differentiation. Significance: The modulation of Pin1 activity may be a clinical target for the regulation of bone formation.

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“…NMP Inhibits RANKL-induced ERK Pathway ActivationGrowth factors that stimulate ERK may ultimately control the activity of c-Fos and AP-1-dependent transcription (25). Recently, it was reported that MIP1␣ (macrophage inflammatory protein 1␣) induces osteoclast formation by activating the MEK/ERK/c-Fos pathway (26) and that vitamin E inhibits RANKL-induced osteoclast differentiation from precursors by suppression of c-Fos expression, possibly through inhibiting ERK (27).…”

Section: Nmp Inhibits Nfatc1 and C-fos Expression And Decreases Ap-1 mentioning

confidence: 99%

Inhibition of Osteoclast Differentiation and Bone Resorption by N-Methylpyrrolidone

Ghayor

Correro

Lange

et al. 2011

Journal of Biological Chemistry

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Regulation of RANKL (receptor activator of nuclear factor B ligand)-induced osteoclast differentiation is of current interest in the development of antiresorptive agents. Osteoclasts are multinucleated cells that play a crucial role in bone resorption. In this study, we investigated the effects of N-methylpyrrolidone (NMP) on the regulation of RANKL-induced osteoclastogenesis. NMP inhibited RANKL-induced tartrate-resistant acid phosphatase activity and the formation of tartrate-resistant acid phosphatase-positive multinucleated cells. The RANKL-induced expression of NFATc1 (nuclear factor of activated T cells, cytoplasmic 1) and c-Fos, which are key transcription factors for osteoclastogenesis, was also reduced by treatment with NMP. Furthermore, NMP induced disruption of the actin rings and decreased the mRNAs of cathepsin K and MMP-9 (matrix metalloproteinase-9), both involved in bone resorption. Taken together, these results suggest that NMP inhibits osteoclast differentiation and attenuates bone resorption. Therefore, NMP could prove useful for the treatment of osteoporosis or other bone diseases associated with excessive bone resorption.Bone remodeling is a physiological process that involves the resorption and synthesis of bone by osteoclasts and osteoblasts, respectively (1, 2). Osteoclasts are known to be formed by the fusion of hematopoietic cells of the monocyte-macrophage lineage during the early stage of the differentiation process (3). This process consists of multiple steps, including differentiation of osteoclast precursors into mononuclear osteoclasts, fusion of mononuclear preosteoclasts into mature multinucleated osteoclasts, and activation of osteoclasts to resorb bone (4 -7). The terminal differentiation in this lineage is characterized by acquisition of mature phenotypic markers such as expression of tartrate-resistant acid phosphatase (TRAP), 2 the calcitonin receptor, MMP-9, and cathepsin K, as well as morphological conversion into large multinucleated cells and the ability to form resorption lacunae on bone (8 -10). The essential signaling molecules for osteoclast differentiation include RANKL and M-CSF (macrophage colony-stimulating factor) in bone marrow-derived macrophage precursor cells (11,12).RANKL is a member of the TNF superfamily that is expressed in osteoblasts. It interacts with the osteoclast cell surface receptor RANK, which in turn recruits TNF receptor-associated factors and plays a crucial role in the osteoclast differentiation axis (13,14). The downstream intracellular signaling mediated by RANK in osteoclast progenitor cells includes TRAF6 (TNF receptor-associated factor 6)-dependent activation of NF-B via the IB kinase complex and MAPKs such as ERK, p38 MAPK, and JNK (7,11,15). In addition, RANKL induces the key transcription factors for osteoclastogenesis, NFATc1 and c-Fos (9, 16, 17). Therefore, chemical or natural compounds that specifically inhibit these steps could be developed as antiresorptive drugs for the treatment of metabolic bone disorders characterized by e...

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Regulation of the Transcriptional Activity of c-Fos by ERK

Cited by 253 publications

References 17 publications

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Negative regulation of Pim-1 protein kinase levels by the B56β subunit of PP2A

Prolyl Isomerase Pin1-mediated Conformational Change and Subnuclear Focal Accumulation of Runx2 Are Crucial for Fibroblast Growth Factor 2 (FGF2)-induced Osteoblast Differentiation

Inhibition of Osteoclast Differentiation and Bone Resorption by N-Methylpyrrolidone

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