Transcriptional Control in Human Diseases

**19**

**Chapter 2**

Signaling

*Eulàlia de Nadal*

**Abstract**

chromatin

**1. Introduction**

Shaping the Transcriptional

Landscape through MAPK

*Gerard Martínez-Cebrián, Francesc Posas and* 

gene expression in organisms ranging from yeast to mammals.

diabetes, inflammatory, and immune response diseases.

A change in the transcriptional landscape is an equilibrium-breaking event important for many biological processes. Mitogen-activated protein kinase (MAPK)

signaling pathways are dedicated to sensing extracellular cues and are highly conserved across eukaryotes. Modulation of gene expression in response to the extracellular environment is one of the main mechanisms by which MAPK regulates proteome homeostasis to orchestrate adaptive responses that determine cell fate. A massive body of knowledge generated from population and single-cell analyses has led to an understanding of how MAPK pathways operate. MAPKs have thus emerged as fundamental transcriptome regulators that function through a multilayered control of gene expression, a process often deregulated in disease, which therefore provides an attractive target for therapeutic strategies. Here, we summarize the current understanding of the mechanisms underlying MAPK-mediated

**Keywords:** MAP kinases, signal transduction, transcription, gene expression,

The intracellular matrix is physically separated from the dynamic extracellular environment; however, their functions are intimately coordinated in order to ensure cell adaptation and survival. Mitogen-activated protein kinase (MAPK) cascades sense and integrate extracellular cues through sequential activation of protein kinases. These highly conserved transduction pathways are involved in a myriad of fundamental cellular processes and determine cell fate. Misregulation of these signaling cascades has major consequences for numerous diseases such as cancer,

About 300 genes encode signaling proteins directly involved in signal transduction, including their positive and negative regulators as well [1]. Upon cell stimulation, in order to adapt to an extracellular insult, these seemingly simple linear signaling pathways harbor the potential to target a large number of substrates of which many are involved in gene expression. In fact, MAPKs control every step studied to date of the highly dynamic process of gene expression. The overall

*Mariona Nadal-Ribelles, Carme Solé,* 
