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Coevolution of RAC Small GTPases and their Regulators GEF Proteins.

Published version
Peer-reviewed

Repository DOI


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Authors

Jiménez-Sánchez, Alejandro 

Abstract

RAC proteins are small GTPases involved in important cellular processes in eukaryotes, and their deregulation may contribute to cancer. Activation of RAC proteins is regulated by DOCK and DBL protein families of guanine nucleotide exchange factors (GEFs). Although DOCK and DBL proteins act as GEFs on RAC proteins, DOCK and DBL family members are evolutionarily unrelated. To understand how DBL and DOCK families perform the same function on RAC proteins despite their unrelated primary structure, phylogenetic analyses of the RAC, DBL, and DOCK families were implemented, and interaction patterns that may suggest a coevolutionary process were searched. Interestingly, while RAC and DOCK proteins are very well conserved in humans and among eukaryotes, DBL proteins are highly divergent. Moreover, correlation analyses of the phylogenetic distances of RAC and GEF proteins and covariation analyses between residues in the interacting domains showed significant coevolution rates for both RAC-DOCK and RAC-DBL interactions.

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Keywords

Coevolution, DBL, DOCK, GEF proteins, RAC, Small GTPases

Journal Title

Evol Bioinform Online

Conference Name

Journal ISSN

1176-9343
1176-9343

Volume Title

12

Publisher

SAGE Publications
Sponsorship
A.J.S. was supported by the Mexican National Council of Science and Technology (CONACyT), the Mexican Secretariat of Public Education (SEP), and the Cancer Research UK.