iBB

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P2) is crucial to many cellular processes in eukaryotes, including membrane trafficking, signal transduction, ion channel function  and cytoskeleton dynamics. This function multiplicity is partially achieved through a dynamic spatiotemporal organization of PI(4,5)P2 within the membrane. In a recent paper published in IJMS, an IBB team (Maria J. Sarmento, Luís Borges-Araújo, Sandra N.Pinto, Nuno Bernardes, Joana Ricardo, Ana Coutinho, Manuel Prieto and Fábio Fernandes) was able to quantify PI(4,5)P2 confinement in living cells making use of FRET imaging measurements. PI(4,5)P2 was found to be significantly compartmentalized at the plasma membrane of HeLa cells. These PI(4,5)P2 enriched domains were shown to not depend on cholesterol content, ruling out an association with lipid rafts. On the other hand, upon inhibition of actin polymerization, compartmentalization of PI(4,5)P2 was almost entirely eliminated, confirming that the cytoskeleton network is the critical component responsible for the formation of nanoscale PI(4,5)P2 domains.

The bacterial protein azurin shows an unexpected therapeutic effect against various types of cancer. This property seems to result from its unique structural and surface features. A 28-residue peptide (named p28) derived from the middle part of azurin has been subjected to various studies and reached two clinical trials phase I in US. In a recent paper published in Biomedicines, a iBB team (Ana Rita Garizo, Lígia Coelho, Sandra Pinto, Tiago Dias, Fábio Fernandes, Nuno Bernardes and Arsénio M Fialho) were able to identified another anticancer bioactive peptide (CT-p19LC) derived from the C-terminal of azurin. CT-p19LC proved to interact preferentially with cancer cells, causing a significative inhibition of cell proliferation in a dose dependent manner. Moreover, it is proposed that the mode of action of CT-p19LC involves perturbation or disruption of cancer cell membranes. Overall this study highlights the relevance of azurin as a source of bioactive peptides with potential application in cancer therapies.