engleski

Structure and function of cancer-related Developmentally regulated GTP-binding protein 1 (DRG1) is conserved between sponges and humans

Cancer is a disease caused by errors within the multicellular system and it represents a major health issue in multicellular organisms. Although cancer research has advanced substantially, new approaches focusing on fundamental aspects of cancer origin and mechanisms of spreading are necessary. Comparative genomic studies have shown that most genes linked to human cancer emerged during the early evolution of Metazoa. Thus, basal animals without true tissues and organs, such as sponges, might be an innovative model system for understanding the molecular mechanisms of proteins involved in cancer biology. One of these proteins is Developmentally regulated GTP-binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). This study reveals a high evolutionary conservation of DRG1 gene/protein in metazoans. Biochemical analysis and structural predictions demonstrate that recombinant DRG1 from humans and sponge Eunapius subterraneus are predominantly monomers that form complexes with DFRP1 and bind non- specifically to RNA and DNA. Our transfection experiments show the intracellular localization of exogenous sponge and human DRG1 in human tumor cells. We reveal the conservation of sponge and human DRG1 biological features, including DRG1:DFRP1 binding, function of DRG1 in α-tubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization of human cancer cells. These results suggest that the ancestor of all Metazoa already possessed DRG1 that is structurally and functionally similar to the human DRG1, even before the development of real tissues or tumors, indicating an important function of DRG1 in fundamental cellular pathways.

cancer, DRG1, sponges

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