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bioRxiv · 10.1101/562173

ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (Cfp1)

Karra, A. S.·Klein, A. M.·Earnest, S.·Stippec, S.·Wichaidit, C.·McGlynn, K.·Trudgian, D. C.·Mirzaei, H.·Cobb, M. H.
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Abstract

BackgroundThe 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.\n\nResultsWe 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 substrate in vitro and 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.\n\nConclusionOur work highlights ERK1/2 interactions with chromatin regulators that contribute to MAPK signaling diversity in the nucleus.

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Karra, A. S., Klein, A. M., Earnest, S., Stippec, S., Wichaidit, C., McGlynn, K., Trudgian, D. C., Mirzaei, H., Cobb, M. H.. 2019-03-08. ERK2 phosphorylates the epigenetic regulator CXXC-finger protein 1 (Cfp1). https://doi.org/10.1101/562173

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