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Chapter Category: Signal Transduction
From the book MSKs
Role of Mitogen and Stress Activated Kinases in Histone Phosphorylation
Brojan Drobic, Beatriz Pérez-Cadahía, Protiti Khan, Shannon Healy and James Davie
Mitogen‑ and stress‑activated protein kinases, MSK1 and MSK2, are activated by the RAS‑MAPK (RAS‑RAF‑MEK‑ERK) and p38 MAPK pathways, and mediate the primary response by connecting mitogenic and stress extracellular stimuli with immediate‑early gene expression. MSK1/2 substrates include histone H3, nucleosome‑binding protein HMGN1, and transcription factors such as the p65 subunit of NF‑κB, ATF1, ER81 and CREB. MSK‑induced H3 phosphorylation at serine 10 and serine 28 is a crucial intermediate step conveying a signal received by a cell‑surface receptor to specific promoters thus triggering chromatin remodeling and transcriptional reprogramming. The outcome of H3 phosphorylation varies with the stimuli and cellular contexts. In cancer cell lines, persistent activation of signaling pathways resulting in elevated steady‑state levels of H3 phosphorylation correlates with abnormal gene expression and uncontrolled growth or metastasis. In postmitotic neurons, H3 phosphorylation plays a role in award‑related and behavioral learning, and long‑term memory processes. In this chapter we review the role of MSK induced histone H3 phosphorylation in normal and disease processes.
- ISBN: TBA
- Publication date: August 1, 2012
- Series: Intelligence Unit
MSKs
Edited by: J. Simon C. Arthur
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