Projectes

The scientific community has broadly accepted the key role of the complex formed by cyclins and CDKs. Nevertheless, it exists a broad variety of cyclins and CDKs with apparently redundant function. The importance and the role of this redundancy are not understood in the physiology of a living cell, especially when the elimination of some of them produces a non-evident phenotype.

Saccharomyces cerevisiae controls G1 progression by means of two different families of cyclins (Cln and Pcl families) and two CDK’s (Cdc28 and Pho85). We want to answer the question of the functional redundancy of the different CDK’s complexes controlling G1. Using S. cerevisiae as a model, we want to demonstrate that Pcl/Pho85 complex has specific substrates, regulates specific functions and is differently regulated to the other cyclin/CDK complex (Cln/Cdc28) in eukaryotic cells. We want to uncover the physiological relevance of the Pcl/Pho85 complexes in non-standard lab conditions expecting an essential role in such more “real” environments. We also want to demonstrate that some of the substrates and regulatory functions of the CDK/Pcl complex are evolutionary conserved in human cells. In this context, it must be noted that the human genome sequence project has unveiled the presence of a whole plethora of new cyclins with unknown functions, showing structural differences with the canonical ones but, surprisingly, very similar to the yeast Pcls. We have obtained results supporting the idea that the newly discovered Pcl-like cyclins are responsible for carrying out some new important functions during G1 phase in both yeast and human cells. Our efforts are focused to know more about the role of this new cyclins.

As a consequence of the fluent colaboration with the Martí Aldea’s group at IRB we are contributing to Aldea’s question regarding the regulation of cell size by CDK-cyclin complexes.

The cell cycle in eukaryotic cells is governed by a family of proteins called cyclin-dependent kinases (CDKs). The activity of these CDKs is tightly regulated through their interaction with other proteins known as cyclins.

The Human Genome Project has identified several new or atypical cyclins and new CDKs whose roles have not yet been established.

Our objective is to characterize the role of these mammalian atypical cyclins in both physiological and pathological situations. We are specifically interested in the study of these CDK-Atypical Cyclin complexes in stem cells and cancer.

The polyphosphate (PolyP) project aims to clarify the roles of this molecule in our cells. Although PolyP is historically considered the cellular phosphate storage, it is emerging the view that it plays more specific functions in the context of cell physiology.

Our group has recently unveiled the role of PolyP as the source of phosphate required for the synthesis of the dNTP pool in late G1 and during the S phase in yeast. The results that we have obtained demonstrate that PolyP-deficient cells possess very low levels of dNTPs, which markedly delays the progression through the cell cycle.

Furthermore, our results implicate PolyP in the resistance to UV- and MMS-induced DNA damage. Experiments using human cell line HEK293 and adult human dermal fibroblasts support that PolyP is also able to afford protection against the damage produced by UV light in human cells.

Facing these promising results, we are currently investigating the regulation of PolyP metabolism in human cells, as well as its possible role in the tumor process.