Naslov
Structure, function and evolution of Developmentally regulated GTP-binding protein 1 (DRG1): Lessons learned from studies in sponge and humans

Autori
Dominko, Kristina ; Talajić, Antea ; Beljan, Silvestar ; Hloušek-Kasun, Andrea ; Škrobot Vidaček, Nikolina ; Herak Bosnar, Maja ; Vlahoviček, Kristian ; Ćetković, Helena

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Skup
The Biochemistry Global Summit – the 25th IUBMB, 46th FEBS and 15th PABMB Congresses

Mjesto i datum
Lisabon, Portugal, 9-14.07.2022

Vrsta sudjelovanja
Predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cancer, DRG1, sponges

Sažetak
Cancer is a disease of multicellular organisms caused by errors within the multicellular system. 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/proteins linked to human cancer emerged during the early evolution of Metazoa. One of these proteins is Developmentally regulated GTP- binding protein 1 (DRG1), a GTPase stabilized by interaction with DRG family regulatory protein 1 (DFRP1). In this study, analysis of DRG1 gene/protein evolutionary history shows its high conservation in metazoans, from sponges (Porifera), basal multicellular animals without true tissues and organs, to humans. Our biochemical analysis and structural predictions imply that both recombinant sponge and human DRG1 are predominantly monomers that form complexes with DFRP1 and bind nonspecifically to RNA and DNA. We reveal the evolutionary conservation of sponge and human DRG1 biological features, including intracellular localization and DRG1:DFRP1 binding, function of DRG1 in αtubulin dynamics, and its role in cancer biology demonstrated by increased proliferation, migration and colonization in human cancer cells. This study indicates 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 tumorigenesis, suggesting an important function of DRG1 in one of the fundamental cellular pathways.

Izvorni jezik
Engleski

Znanstvena područja
Biologija

POVEZANOST RADA