Grant: Travel Awards - Institute Community Support

Rvb1 and Rvb2 are critical proteins involved in several cellular activities, assisting the assembly of protein complexes and contributing to the normal cellular physiology. Deregulation of Rvb1 and Rvb2 are frequently associated with a wide variety of cancers, such as liver, colorectal, lung, renal, breast, gastric and leukemia. Due to these aspects, Rvb1 and Rvb2 have been shown as good targets for therapeutics. Several roles has been attributed to individuals Rvb1 and Rvb2 proteins, however our work suggests that the two proteins work mainly together, depending on each other to execute their activities in the cell. We found that Rvb1 and Rvb2 act basically in the same pathways in the cell and their activities in vitro are greater when they associate. Structural analyses revealed that three molecules of Rvb1 associate with three molecules of Rvb2, forming a hexamer with an alternating layout. Cellular studies showed that Rvb1 and Rvb2 strongly colocalize and during nutrient depletion conditions a fraction of these proteins group together to form foci structures close to the cell nucleus. Such foci do not localize with other similar aggregates or granules and are dissolved upon nutrient addition. We propose that Rvb1 and Rvb2 foci are critical storage structures for these proteins under specific cellular conditions. Altogether, our work pointed out that Rvb1 and Rvb2 exert their roles mainly together and during specific stressful conditions their form foci structures. Such findings are novel and important aspects of Rvb1 and Rvb2 biology, helping to understand how these proteins behave in normal and stressed eukaryotic cells.