1 This forces restore NAD + / NADH (H + ) by conversion of pyruvate to lactate, which is released into the extracellular medium, from which is taken up by neurons and convert it into pyruvate and used as energy source in mitochondria. Thus, glycolytic metabolism of astrocytes preferably cooperates with neurons allowing glucose to intended purposes and protecting antioxidants apoptosis. 2 In addition, this mechanism could also be very relevant in cancer, where it operates a similar mechanism of metabolic regulation.

It remains to know if the way CDH1-Pfkfb3 described is subject to physiological regulation in vivo. It is known that CDH1, known for its role in genome stability and tumor suppression, is inhibited by phosphorylation in neurons during glutamatergic stimulation. 3 neurotransmission may be coupled through CDH1, the regulation of neuronal glycolysis through mechanisms that require further investigation. Given the importance of carbohydrate metabolism has on neuronal survival, knowledge of these mechanisms could help to establish new molecular targets to take into account neurological disorders.

He returned to Salamanca, where he is now professor at the university. Among its main points highlights the identification of cytochrome c oxidase as a primary target of nitric oxide, and regulation of glutathione metabolism in neural cells in relation to the protection of neuronal damage. His group is working on mechanisms regulating neuronal bioenergetics, its relevance to oxidative stress and its relation to the identification of molecular targets in Parkinson’s disease and other neurodegenerative diseases.

This paper has analyzed the enzymatic function PIG3 finding that has NADPH-dependent reductase activity against ortoquinonas. However, this reductase activity is much lower than that of the ζ-crystalline (quinone reductase). Furthermore, these investigators have described the crystal structure of the PIG3, which has enabled the identification of the cofactor binding sites, the substrates and possesses conserved residues from bacteria to humans. Moreover, it has been suggested that Tyr-59 of the ζ-crystalline (Tyr-51 in PIG3) is involved in catalyzing the reduction of quinone.

Kinetic studies with mutant Tyr / Phe and Tyr / Ala in both enzymes have shown that Tyr is not in the catalytic center, but participates in substrate binding and is consistent with a mechanism based on the effects of proximity. Moreover, the contribution of PIG3 in apoptosis may be through the generation of oxidative stress. PIG3 overexpression systems in vitro and in vivo accumulates reactive oxygen species (ROS). Similarly, an inactive mutant of PIG3 (S151V) did not produce ROS in cells, indicating that enzymatically active protein is required for this function. With this the authors conclude that PIG3 action is via oxidative stress resulting from its enzymatic activity.

Currently known to exert a role in maintaining the level of endoplasmic reticulum (ER), controlling the Ca 2 + homeostasis and in regulating the response of the protein is not folded (UPR: unfolded protein response) on a non-apoptotic. The ER and mitochondria are physically and functionally connected. It has accepted that the mitochondrial expression of BAX and BAK was sufficient to initiate apoptosis and it was unclear if the corresponding ER BAK and BAX could have similar potential.

Using cells expressing BAK only in reticulum, the Pimentel-Muiños group, Center for Cancer Research at the University of Salamanca, has identified the proapoptotic protein BCL-2 family that can activate the mitochondrial pathway of death also when are restricted only in the ER. This means that with the involvement of protein mediators of type BH3-only (Puma and Bim) can produce apoptosis of multidomain BAK using lattice. This paper shows how through cascades unconventional space restriction is overcome by cellular signaling components, plus the discovery that mitochondria and ER can communicate during apoptosis, provides new insights into the regulation of cell death.

In this study we have identified gene mutations that cause a decrease TARBP2 of TRBP protein expression and a defect in the processing of microRNA. A series of experiments revealed that the TARBP2 gene was mutated in 26% (72 cases of the 282 samples) of human tumors analyzed. These mutations have been found in both sporadic and hereditary carcinomas that are characterized by a defect in the repair of small errors in DNA and its progression is due to the ease to produce mutations. Moreover, the reintroduction of the TRBP gene restores the production of microRNAs and inhibits tumor growth. It should be noted also that TRBP dysfunction is associated with a destabilization of the protein DICER1. Taken together, these results explain that during tumorigenesis there is a loss of function of regulating the processing machinery of the microRNA.

Cyclin A accumulates at the beginning of S phase, contributing to the stimulation of DNA synthesis. Then the level of cyclin A remains high during G2 and is degraded in prometaphase. Cyclin B levels increase during G2 and is then binds to CDK1. This complex leads to the metaphase cycle where cyclin B is degraded, although much later than cyclin A. Signals that dictate cyclin degradation in prometaphase are still controversial. In this study of Matthew et al., Department of Cell Biology, University of Barcelona, we show that cyclin A can be acetylated in vivo and in vitro by an acetyltransferase P / CAF in four lysines located at the N-terminal .

In mitosis maximum acetylation occurs simultaneously to ubiquitination, which marks the importance of acetylation on the stability of cyclin A In addition, cells were treated with inhibitors of histone deacetylases, acetylation of cyclin A increases and stability decreases, which confirms the role of acetylation in the degradation of cyclin A. In summary, the specific acetylation of certain lysines of cyclin A is crucial for the stability of the same and has a role regulating the activity of cdk-cyclin pair A.

The peripheral protein AKAP450 enlists the GM130, which in turn binds to a g-Turkish, giving a capacity of nucleation cis-Golgi compartment. Therefore, the AKAP450, a protein localized in both the centrosome and in GA, acts as a general regulator of MT nucleation cell. The study by Rivero et al., Department of Cellular Signaling CABIMER-CSIC, Seville, explains the functional differences between GA and microtubules of the centrosome in regard to polarization and cell migration. Those cells lacking the AKAP450 in GA, but not in the centrosome, can not migrate, however, retain the ability to reorient its centrosome and Golgi membranes to the end of the cell.

It appears that the microtubules nucleated in GA have specific effects on cell migration, this being independent of the centrosome and Golgi cell positioning motor. However, the direct role of AKAP450 in migration and cell polarization through a mechanism independent of microtubules can not be excluded. Further studies will determine how the microtubules nucleated in the GA control this cell migration and whether they can regulate other cellular processes.

The α6β4-plectina interaction is essential for the stability of the hemidesmosome and is believed to be the start of assembly of these adhesion complexes that anchor epithelial cells to the basement membrane. Most α6β44 interactions occur through the cytoplasmic half of the β4 subunit. The N-terminal region of plectina this subunit interacts with β4 in multiple zones. Two mutations in the gene for β4 (ITBG4) introduce R1225H and R1281W substitutions in one of the domains of β4 that prevent binding to plectina and lead to nonlethal forms of epidermolysis bullosa.

These researchers led by de Pereda, University of Salamanca, have determined the structure of the complex primary α6β4-plectina. Combining mutagenesis and biophysical data have identified the critical elements of this interaction. They have also solved the crystal structure of the β4 subunit in the absence of plectina. This can confirm a conformational change b4 segment before joining plectina and suggests a form of allosteric control of integrin. These findings provide the molecular basis of certain diseases in which the targets are the assembly and stability of hemidesmosomes.

From these investigations, Massagué’s group had isolated cells preferentially infiltrate the brain from patients with advanced cancer. Through the analysis of gene expression in these cells and clinical samples, and corresponding functional analysis has identified some 243 genes. Were selected those whose overexpression in breast tumors are associated with a relapse in the brain (brain relapse) and have identified mediators of cancer cells pass through the blood brain barrier. It is concluded that the gene for cyclooxygenase COX-2 and ligand factor receptor (EGFR: epidermal growth factor receptor) or HBEGF are most important.

These genes had been found in tumor cells infiltrated the lungs, breast, but not in bone or liver, indicating that they are mediators of brain and lung metastases. We also have found a brain metastasis-specific gene, that of α-2 ,6-sialyl (ST6GALNAC5). The sialyl catalyze the transfer of sialic acid units to gangliosides and glycoproteins. The protein sialización power not only adherence to the endothelial cells of the brain, but its passage through the blood-brain.

He is a researcher at the Howard Hughes Medical Institute, member of the National Academy of Sciences and the Institute of Medicine and holds the Chair Alfred P. Sloan. Since 2005, is deputy director of IRB Barcelona, Barcelona Science Park (PCB), its mission is to develop competitive research programs, incorporating leading scientists and policymakers advanced research.

She also oversees a laboratory dedicated to the study of cancer metastasis, the MetLab. Among the many awards received is the Prince of Asturias Prize (2004) and the prize GHA Clowes Memorial Award presented by the American Association for Cancer Research (2008) and, last June, the prize BBVA Foundation Frontiers of Knowledge in the category in Biomedicine. The work of Massagué’s group has focused on studying the control of cell growth and metastasis in cancer.