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Tag: p38γ (Page 1 of 3)

Stress-activated kinases signaling pathways in cancer development

Leticia Herrera-Melle, María Crespo, Magdalena Leiva & Guadalupe Sabio.

Cancer is a large group of diseases characterized by abnormal cell growth that can lead to metastasis. It is the second leading cause of death worldwide, and its incidence is expected to rise over the next decades. Stress-activated protein kinases (SAPK) are important players in its regulation. Several studies have tried to unravel their role; however, their pro-tumorigenic or anti-tumorigenic properties are sometimes controversial.

JNK control of tumor microenvironment
JNK control of tumor microenvironment.

In this review, we will discuss the main roles of the different SAPK in the control of tumor development through essential processes such as cell proliferation, apoptosis or invasiveness. We will also show the latest discoveries regarding the contribution of SAPK in shaping tumor microenvironment through the regulation of organ crosstalk and immune cell response during cancer progression.

All these studies are relevant examples of how SAPK offer new therapeutic avenues for cancer patients that may help increase their survival.

p38γ is essential for cell cycle progression and liver tumorigenesis

Antonia Tomás-Loba, Elisa Manieri, Bárbara González-Terán, Alfonso Mora, Luis Leiva-Vega, Ayelén M. Santamans, Rafael Romero-Becerra, Elena Rodríguez, Aránzazu Pintor-Chocano, Ferran Feixas, Juan Antonio López, Beatriz Caballero, Marianna Trakala, Óscar Blanco, Jorge L. Torres, Lourdes Hernández-Cosido, Valle Montalvo-Romeral, Nuria Matesanz, Marta Roche-Molina, Juan Antonio Bernal, Hannah Mischo, Marta León, Ainoa Caballero, Diego Miranda-Saavedra, Jesús Ruiz-Cabello, Yulia A. Nevzorova, Francisco Javier Cubero, Jerónimo Bravo, Jesús Vázquez, Marcos Malumbres, Miguel Marcos, Sílvia Osuna & Guadalupe Sabio.

The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)–cyclin protein complex. However, control of the G0-to-G1 transition is not completely understood.

Mitosis in liver
Mitosis in hepatocytes (Photo: Alfonso Mora/CNIC).

Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues.

Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease.

CICERONE program 2019 for Masters and advanced undergraduate students

As in previous years, our group is open to master and advanced undergraduate students for extending their scientific training through hands-on experience in our laboratory during the summer recess (1 July – 30 September). In addition to carrying out a supervised research project, the students will also attend CNIC seminars.

The aim of the CICERONE program is to give university students first-hand knowledge of biomedical research so that they can make more informed choices about the possibility of pursuing a scientific career.

To apply, you must register at CNIC website before 15 April 2019.

Link Size
2019 Guidelines 348 KB
Document of acceptance 1.53 MB
Call extract from BOE 171 KB

For the 2019 call, we are offering the following research projects:

  • Role of p38MAPK in metabolic diseases: Metabolic syndrome is a medical disorder defined by the co‐occurrence of obesity, impaired glucose tolerance, dyslipidemia and hypertension. Stress activated protein kinases have been shown to control both obesity by itself and diabetes associated to obesity. These stress kinases are activated by several MAPK activated kinases (MKK). We want to investigate the role of MKK3 in this process and the molecular mechanism by which this kinase could affect diabetes.
  • p38MAPK in heart physiology: The p38MAPK pathway transduces a variety of extracellular signals regulating cellular responses to stress, being implicated in cell proliferation, differentiation and apoptosis. Its implication in the development of human diseases it is being deeply studied. Four p38MAPK family members have been identified: p38α, β, γ and δ. Preliminary data from our laboratory show that these kinases may control cytokine production during acute and chronic inflammatory processes. Moreover, studies with genetically modified mice made in our laboratory confirm that p38MAPKs have a role in the development of the heart. Our main objective is to determine if the regulation of the p38MAPK signalling pathway could have beneficial effects in the cardiac response to exercise.
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