Abstract
Elk-1 is a transcription factor that binds together with a dimer of the serum response factor (SRF) to the serum-response element (SRE), a genetic element that connects cellular stimulation with gene transcription. Elk-1 plays an important role in the regulation of cellular proliferation and apoptosis, thymocyte development, glucose homeostasis and brain function. The biological function of Elk-1 relies essentially on the interaction with other proteins. Elk-1 binds to SRF and generates a functional ternary complex that is required to activate SRE-mediated gene transcription. Elk-1 is kept in an inactive state under basal conditions via binding of a SUMO-histone deacetylase complex. Phosphorylation by extracellular signal-regulated protein kinase, c-Jun N-terminal protein kinase or p38 upregulates the transcriptional activity of Elk-1, mediated by binding to the mediator of RNA polymerase II transcription (Mediator) and the transcriptional coactivator p300. Strong and extended phosphorylation of Elk-1 attenuates Mediator and p300 recruitment and allows the binding of the mSin3A-histone deacetylase corepressor complex. The subsequent dephosphorylation of Elk-1, catalyzed by the protein phosphatase calcineurin, facilitates the re-SUMOylation of Elk-1, transforming Elk-1 back to a transcriptionally inactive state. Thus, numerous protein–protein interactions control the activation cycle of Elk-1 and are essential for its biological function.
Highlights
Accepted: 5 October 2021The human genome encodes more than 1500 transcription factors
In this article we discuss the molecular mechanism of the transcriptional activation of the stimulus-responsive transcription factor Elk-1, which is essentially involved in the control of cellular proliferation induced by mitogens, in thymocyte development, glucose homeostasis and brain function
We focus on the essential role of numerous protein–protein interactions for the activation of Elk-1, involving several protein kinases, a Ca2+ /calmodulin-dependent protein phosphatase, chromatin modifiers and the transcription factor serum response factor (SRF), which all work in a sequential manner
Summary
The human genome encodes more than 1500 transcription factors These proteins have a modular structure with distinct domains for DNA binding and transcriptional activation (or repression). Stimulus-responsive transcription factors connect cellular stimulation with gene transcription, involving protein kinases as signal transducers. These transcription factors contain phosphorylation-responsive activation domains, that is, transcriptional activation requires phosphorylation. We focus on the essential role of numerous protein–protein interactions for the activation of Elk-1, involving several protein kinases, a Ca2+ /calmodulin-dependent protein phosphatase, chromatin modifiers and the transcription factor SRF, which all work in a sequential manner. Molecules 2021, 26, 6125 a Ca2+/calmodulin-dependent protein phosphatase, chromatin modifiers and the transcription factor SRF, which all work in a sequential manner
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