‎Ne‎w results on the fu‎nction of the tumor suppre

来源:kmgdwlc.com   作者:   发表时间:2020-02-21 03:43:50

The study analyzes the mechanisms that regulate some molecular signaling pathways related to carcinogenesis and tumor progression and opens new perspectives to the fight against human cancer.

Among the participants in the new study, led by Professor José Luis Rosa, are the researchers Leonardo Pedrazza, Taiane Schneider, Ramon Bartrons and Francesc Ventura, from the Department of Physiological Sciences of the UB and IDIBELL.

How does HERC1 ligase regulate the activation of ERK and p38 kinase?

MAPK proteins and the regulator kinases—MAPKK and MAPKKK—take part in intracellular signaling cascades such as the RAF/MEK/ERK pathway, which controls the essential cell processes (growth, proliferation, differentiation, survival and cell migration). Dysfunctions in the regulation of these molecular signaling pathways can alter the physiological cycle of the cell and therefore generate tumor proliferation and growth.

The published study in the journal Scientific Reports describes for the first time how the HERC1 enzyme—ubiquitin ligase—is able to regulate the process of cell migration through the MKK/p38 signaling pathway, regulated by the C-RAF factor.

The new study expands the knowledge on the tumor-suppressor role of HERC proteins (ubiquitin ligase); enzymes that regulate the function of some proteins involved in processes such as cell growth and proliferation through its molecular marking with ubiquitin molecules (ubiquitination). In particular, the new study reveals HERC1 ligase is able to regulate the activation of ERK and p38 kinase through the union of ubiquitin molecules with the C-RAF factor.

According to the authors, the discovery of an unexpected communication between RAF proteins and MKK3/p38 pathway opens new perspectives regarding future therapeutical targets in the fight against human cancers.

Moreover, the research group has a distinguished experience in the study of HERC proteins and their link to several pathologies (cancer, ataxia, etc.). In previous studies, the team contributed to the functional characterization of two ubiquitin kinases—HERC1 and HERC2 (Frontiers in Oncology, 2019)—and the description of the role of HERC1 ligase in the regulation of the cell proliferation through the activation of the ERK signaling pathway through a mechanism that affects ubiquitination and degradation of C-RAF (Oncotarget, 2018).

HERC2 ligase and regulation of p5 protein, tumor suppressor

In another study, which was published in the journal Molecular Oncology, the experts of the UB and IDIBELL stated that Mdm2 protein —the main regulator of the p53 protein, tumor suppressor—is part of the ternary complex known as p53-HERC2-NEURL4. The authors of this study are the experts Jesús García Cano, Susana Sánchez Tena, Joan Sala Gaston, Agnès Figueras, Francesc Viñals, Ramon Bartrons and Francesc Ventura, under the supervision of Professor José Luis Rosa.


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