C3G self-regulatory mechanism revealed: implications for hematopoietic malignancies

Arturo Carabias; Carmen Guerrero; José M de Pereda

doi:10.1080/23723556.2020.1837581

C3G self-regulatory mechanism revealed: implications for hematopoietic malignancies

Mol Cell Oncol. 2020 Dec 1;8(1):1837581. doi: 10.1080/23723556.2020.1837581.

Authors

Arturo Carabias^{1

2}, Carmen Guerrero^{1

3}, José M de Pereda¹

Affiliations

¹ Centro de Investigación del Cáncer and Instituto de Biología Molecular y Celular del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)- Universidad de Salamanca, Salamanca, Spain.
² Structural Molecular Biology Group, Novo Nordisk Foundation Centre for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark.
³ Departamento de Medicina, Facultad de Medicina, Universidad de Salamanca, Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain.

Abstract

Abnormally increased signaling by the GTPase RAP1 favors progression of diverse tumors. We have characterized the auto-regulation and activation of C3G (RAPGEF1), an activator of RAP1. This led us to discover mutations in non-Hodgkin's lymphomas that activate C3G-RAP1 constitutively, suggesting that deregulation of C3G may favor the dissemination of tumor cells.

Keywords: RAP1; RAPGEF1; guanine nucleotide exchange factor; non-Hodgkin’s lymphoma; signaling.

Grant support

The work described in this Auto Commentary was supported by the Spanish Ministry of Science and Innovation (MCINN), Agencia Estatal de Investigación, and the European Regional Development Fund (ERDF) [grants BFU2015-69499-P, PID2019-105763GB-I00, SAF2016-76588-C2-2-R, PID2019-104143RB-C21]; and from the Consejería de Educación, Junta de Castilla y León [grant SA017U16]. A.C. was funded by MICINN [FPU14/06259]. The authors’ institution is supported by the Programa de Apoyo a Planes Estratégicos de Investigación de Estructuras de Investigación de Excelencia co-funded by Junta de Castilla y León and ERDF [CLC-2017-01].