Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1)

Janknecht, Ralf

doi:10.1038/sj.onc.1206185

Cited by 93 publications

(73 citation statements)

References 48 publications

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“…The same blot was reprobed with an anti-MSK1 antibody. least in part through its ability to associate with and to phosphorylate the general transcription coactivators CBP/p300 (9). In this study, we demonstrate that TGF-␤ induces the phosphorylation of MSK1 at the activating sites in a p38-dependent manner.…”

Section: Fig 3 P38 Isoform ␣ Is Responsible For Increased Smad3 Tramentioning

confidence: 51%

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Evidence for a Role of MSK1 in Transforming Growth Factor-β-mediated Responses through p38α and Smad Signaling Pathways

Abécassis

Rogier

Vázquez

et al. 2004

Journal of Biological Chemistry

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Smad proteins are central mediators of the transforming growth factor-␤ (TGF-␤) superfamily signaling. The mitogen-activated protein kinase (MAPK) p38 is also one of the downstream targets required for TGF-␤-mediated responses. Although the interplay between the p38 and Smad signaling pathways might allow cells to display diverse patterns of responses to TGF-␤, the mechanism of this cross-talk is not well established. We report here that inhibition of the p38␣ isoform suppressed the ability of Smad3 to mediate TGF-␤-induced transcriptional responses. The inhibition of p38 activity blocked TGF-␤-mediated phosphorylation of the MSK1 kinase, a substrate of p38 that plays an important role in the remodeling of chromatin. Moreover, we observed that expression of dominant-interfering mutants of MSK1 blocked the binding of Smad3 to the coactivator p300 in response to TGF-␤ signaling. These data reveal a new mechanism whereby the Smad signaling pathway and the p38 cascade are integrated in the nucleus to activate gene expression.

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Section: Fig 3 P38 Isoform ␣ Is Responsible For Increased Smad3 Tramentioning

confidence: 51%

“…The MSK1 kinase consists of an N-terminal and a C-terminal catalytic domain, and the activity of both domains is required for function of the protein (8). MSK1 is constitutively localized in the nucleus, where it interacts with the general transcription activators CBP/p300 (9).…”

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confidence: 99%

Evidence for a Role of MSK1 in Transforming Growth Factor-β-mediated Responses through p38α and Smad Signaling Pathways

Abécassis

Rogier

Vázquez

et al. 2004

Journal of Biological Chemistry

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“…Alternatively, H3 phosphorylated at S28 may be a better substrate for the H3 K27 HAT. In support of the first scenario, MSK1 was previously shown to coimmunoprecipitate with multiple HATs, including p300 and cAMP response element binding protein (CREB)-binding protein (CBP) (27), which are known to acetylate H3 at K27 (22). As for the second scenario, we and others have previous shown that the yeast HAT, Gcn5, preferentially acetylates H3S10ph peptides over the unmodified form (4).…”

Section: Discussionmentioning

confidence: 78%

Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing

Lau

Cheung

2011

Proc. Natl. Acad. Sci. U.S.A.

154

166

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Histone H3 phosphorylation is a critical step that couples signal transduction pathways to gene regulation. To specifically assess the transcriptional regulatory functions of H3 phosphorylation, we developed an in vivo targeting approach and found that the H3 kinase MSK1 is a direct and potent transcriptional activator. Targeting of this H3 kinase to the endogenous c-fos promoter is sufficient to activate its expression without the need of upstream signaling. Moreover, targeting MSK1 to the α-globin promoter induces H3 S28 phosphorylation and reactivates expression of this polycomb-silenced gene. Importantly, we discovered a mechanism whereby H3 S28 phosphorylation not only displaces binding of the polycomb-repressive complexes, but it also induces a methylacetylation switch of the adjacent K27 residue. Our findings show that signal transduction activation can directly regulate polycomb silencing through a specific histone code-mediated mechanism.chromatin | gene expression | phospho-acetylation | methylation H 3 phosphorylation is a downstream event for a number of signal transduction pathways in mammalian cells (reviewed in refs. 1 and 2). For example, rapid and transient phosphorylation of H3 at S10 (H3S10ph) is detected at the promoters and coding regions of immediate-early (IE) genes upon stimulation of the MAPK or p38 pathways, suggesting that this signalinginduced histone modification functions to activate transcription of IE genes. Thus far, multiple kinases, including RSK2, MSK1/ 2, PIM1, and IKKα, have been shown to directly phosphorylate H3. As a common target of diverse signaling cascades, H3 phosphorylation is thought to be a critical step translating signal transduction information to the chromatin/transcriptional regulatory machinery (3).Currently, how H3 phosphorylation is mechanistically linked to the transcriptional process is still not fully understood. H3 S10 phosphorylation can be physically coupled to acetylation of nearby lysine residues (K9 or K14), suggesting that combinations of these modifications function together to activate transcription (4-6). Specific isoforms of 14-3-3 directly bind H3S10ph, and this interaction is greatly enhanced by additional acetylation of the nearby K14 residue, further illustrating the biological relevance of specific combinations of histone modifications (7,8). Finally, recruitment of 14-3-3 through H3S10ph at the promoters of HDAC1 and several IE genes is thought to facilitate transcription induction of these genes (7, 9, 10). Binding of 14-3-3 to H3S10ph at the FOSL1 enhancer, which is located downstream of the transcription start site, initiates sequential recruitment of the histone acetyltransferase (HAT) males absent on the first (MOF), the bromodomain-containing protein 4 (BRD4), and the positive transcription elongation factor b (P-TEFb) (10). At least for this particular gene, H3 S10 phosphorylation leads to the release of the preinitiated but paused RNA polymerase II (RNAP II) and facilitates transcriptional elongation. In addition to S10, H3 is a...

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“…In addition, it has been implicated from studies in fibroblasts that p38 MAPK stimulates the transactivation potential of the transcription factor NF-B through a functional interaction with p300/CBP (58). Furthermore, a direct downstream target of p38 MAPK, the mitogen-and stress-activated protein kinase-1 (MSK1), can interact with p300 and CBP to stimulate CBP transactivation function (59). In our study, phosphorylation of MEF-2C by p38 was shown to be important for transactivation of the MyHCIId/x promoter, and the MEF-2C-mediated effect was at least in part dependent on CBP binding to MEF-2 heterodimers.…”

Section: Journal Of Biological Chemistry 7271mentioning

confidence: 70%

The p38α/β Mitogen-activated Protein Kinases Mediate Recruitment of CREB-binding Protein to Preserve Fast Myosin Heavy Chain IId/x Gene Activity in Myotubes

Meißner¹,

Chang

Kubis³

et al. 2007

Journal of Biological Chemistry

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In skeletal muscle, the transformation of fast into slow fiber type is accompanied by shifts in fiber type-specific gene expression that includes down-regulation of the adult fast fiber myosin heavy chain IId/x (MyHCIId/x) gene. Here, we report that the mitogen-activated protein kinases (MAPKs) p38␣/␤ regulate MyHCIId/x gene expression. Electrical stimulation of rabbit skeletal muscle cells with a slow fiber type activity pattern and treatment of C2C12 myotubes with Ca 2؉ -ionophore inhibited p38␣/␤ MAPKs and reduced fast fiber type MyHC protein expression and promoter activity. Pharmacological inhibition of p38␣/␤ also down-regulated MyHCII gene expression. In controls, binding of the myocyte enhancer factor-2 (MEF-2) isoforms C and D as a heterodimer to a proximal consensus site within the MyHCIId/x promoter and recruitment of a transcriptional coactivator, the CREB-binding protein CBP, were observed. Overexpression of wild type MEF-2C but not of a MEF-2C mutant that cannot be phosphorylated by p38 induced promoter activity. Mutation of the MEF-2-binding site decreased the inducing effect of overexpressed CBP. Inhibition of p38␣/␤ MAPKs abolished CBP binding, whereas enforced induction of p38 by activated MAPK kinase 6 (MKK6EE) enhanced binding of CBP and increased promoter activity. Furthermore, knockdown of endogenous CBP by RNA interference eliminated promoter activation by MEF-2C or MKK6EE. In electrical stimulated and Ca 2؉ -ionophore-treated myotubes, CBP was absent in complex formation at that site. Taken together, the data indicate that p38␣/␤ MAPKs-mediated coactivator recruitment at a proximal MEF-2 site is important for MyHCIId/x gene regulation in skeletal muscle.Skeletal muscle fibers have been classified into fiber types based on their contraction speed, force development, fatigability, and metabolic functions (1). The characteristic fiber types are fast twitch glycolytic (type IID/X and IIB), fast twitch oxidative/glycolytic (type IIA), and slow twitch oxidative (type I/␤). Fast fibers express the IID/X, IIB, or IIA isoform of the myosin heavy chain (MyHC), 3 whereas slow fibers predominantly express the type I/␤ isoform. The functional, biochemical, and morphological differences between fiber types are a consequence of different fiber-specific gene expression patterns. Fibers are characterized by a remarkable plasticity and can be modulated by chronic low frequency electrical stimulation depending on the imposed activity pattern (2). Physiologically, this transformation process in fiber type occurs in response to altered demands, such as increases in muscle activity (3). Fiber type shifts are also observed during aging and disease. The importance of changes in intracellular Ca 2ϩ as a trigger for fiber type transformation has clearly been demonstrated by a Ca 2ϩ -ionophore-induced fast-to-slow transformation in primary skeletal muscle cells (4, 5). The involvement of calcineurin, a Ca 2ϩ -calmodulin-regulated serine/threonine phosphatase, in transducing the Ca 2ϩ -signal into altered gene expre...

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Regulation of the ER81 transcription factor and its coactivators by mitogen- and stress-activated protein kinase 1 (MSK1)

Cited by 93 publications

References 48 publications

Evidence for a Role of MSK1 in Transforming Growth Factor-β-mediated Responses through p38α and Smad Signaling Pathways

Evidence for a Role of MSK1 in Transforming Growth Factor-β-mediated Responses through p38α and Smad Signaling Pathways

Histone code pathway involving H3 S28 phosphorylation and K27 acetylation activates transcription and antagonizes polycomb silencing

The p38α/β Mitogen-activated Protein Kinases Mediate Recruitment of CREB-binding Protein to Preserve Fast Myosin Heavy Chain IId/x Gene Activity in Myotubes

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