ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (CFP1)
Abstract Background The Ras-Raf-MEK-ERK signaling pathway is essential for proper development and homeostatic regulation in eukaryotic cells and underlies progression of several types of cancer. Many pathway functions are performed by extracellular signal-regulated kinase (ERK)1 and 2 (ERK1/2), serine/threonine protein kinases of the mitogen-activated protein kinase (MAPK) family that interact with a large number of substrates and are highly active in the nucleus.Results We identified the epigenetic regulator CXXC-finger protein 1 (CFP1) as a protein that interacts with ERK2 on chromatin. CFP1 is involved in multiple aspects of chromatin regulation, including histone methylation and DNA methylation. Here, we demonstrate the overlapping roles for ERK1/2 and CFP1 in regulation of immediate early gene (IEG) induction. Our work suggests multiple modes of co-regulation and demonstrates that CFP1 is required for an optimal signal-dependent response. We also show that CFP1 is an ERK2 substratein vitroand identify several phosphorylation sites. Furthermore, we provide evidence that Su(var)3-9, Enhancer-of-zeste and Trithorax (Set)1b, a CFP1-interacting histone methylase, is phosphorylated by ERK2 and is regulated by CFP1.Conclusion Our work highlights ERK1/2 interactions with chromatin regulators that contribute to MAPK signaling diversity in the nucleus..
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Preprint| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
bioRxiv.org - (2022) vom: 13. Sept. Zur Gesamtaufnahme - year:2022 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Karra, Aroon S. [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.1101/562173 |
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| PPN (Katalog-ID): |
XBI000461687 |
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| 100 | 1 | |a Karra, Aroon S. |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (CFP1) |
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| 520 | |a Abstract Background The Ras-Raf-MEK-ERK signaling pathway is essential for proper development and homeostatic regulation in eukaryotic cells and underlies progression of several types of cancer. Many pathway functions are performed by extracellular signal-regulated kinase (ERK)1 and 2 (ERK1/2), serine/threonine protein kinases of the mitogen-activated protein kinase (MAPK) family that interact with a large number of substrates and are highly active in the nucleus.Results We identified the epigenetic regulator CXXC-finger protein 1 (CFP1) as a protein that interacts with ERK2 on chromatin. CFP1 is involved in multiple aspects of chromatin regulation, including histone methylation and DNA methylation. Here, we demonstrate the overlapping roles for ERK1/2 and CFP1 in regulation of immediate early gene (IEG) induction. Our work suggests multiple modes of co-regulation and demonstrates that CFP1 is required for an optimal signal-dependent response. We also show that CFP1 is an ERK2 substratein vitroand identify several phosphorylation sites. Furthermore, we provide evidence that Su(var)3-9, Enhancer-of-zeste and Trithorax (Set)1b, a CFP1-interacting histone methylase, is phosphorylated by ERK2 and is regulated by CFP1.Conclusion Our work highlights ERK1/2 interactions with chromatin regulators that contribute to MAPK signaling diversity in the nucleus. | ||
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| 700 | 1 | |a Klein, Aileen M. |e verfasserin |4 aut | |
| 700 | 1 | |a Earnest, Svetlana |e verfasserin |4 aut | |
| 700 | 1 | |a Stippec, Steve |e verfasserin |4 aut | |
| 700 | 1 | |a Wichaidit, Chonlarat |e verfasserin |4 aut | |
| 700 | 1 | |a McGlynn, Kathleen |e verfasserin |4 aut | |
| 700 | 1 | |a Trudgian, David C. |e verfasserin |4 aut | |
| 700 | 1 | |a Mirzaei, Hamid |e verfasserin |4 aut | |
| 700 | 1 | |a Cobb, Melanie H. |e verfasserin |4 aut | |
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