Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific substrate of yeast metacaspase.

Yeast metacaspase (Yca1p) is required for the execution of apoptosis upon a wide range of stimuli. However, the specific degradome of this yeast protease has not been unraveled so far. By combining different methodologies described as requisites for a protein to be considered a protease substrate, such as digestome analysis, cleavage of recombinant GAPDH by metacaspase and evaluation of protein levels in vivo, we show that upon H(2)O(2)-induced apoptosis, the metabolic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is a specific target of metacaspase. Nitric oxide (NO) signaling, which mediates H(2)O(2)-induced apoptosis, is required for metacaspase specific GAPDH cleavage. In conclusion, in this work we identified GAPDH as the first direct yeast metacaspase substrate described so far. Although mammalian caspases and yeast metacaspase apparently have distinct target cleavage sites, GAPDH arises as a common substrate for these proteases.

Fish and apoptosis: molecules and pathways.

Apoptosis is a genetically controlled and evolutionarily conserved form of active cell death, albeit with an increase in complexity with continuing development. A high conservation at the functional and molecular level has been described between the players of the apoptotic machinery in invertebrates (Caenorhabditis elegans and Drosophila) and mammals. However, fish represent an excellent and advantageous model for the study of vertebrate development and disease, bridging the gap between the C. elegans/Drosophila and mouse/human models. Moreover, contrary to C. elegans and Drosophila, fish can be used for studying the development and function of vertebrate-specific organs and have a fully developed immune system similar to that of mammals. Last but not less important, both the environment and human health will obviously gain by using the knowledge generated through the use of fish models, for developing better prophylactic and therapeutic measures with impact on the aquaculture industry. In the present article, structural and functional data on the most important apoptosis related molecules, namely death-receptor, Bcl-2 and caspase families, and mechanisms are reviewed. The data point to the existence in fish of apoptotic pathways equivalent to those of mammals, making fish useful animal models for studying apoptosis, which may have great applicability for the advance of the knowledge on the role of apoptotic cell death in human apoptosis-related disorders as well as in pharmaceutical design.

The deletions of 22q11--the Portuguese experience.

The patients with a chromosome 22q11 deletion have a variable phenotype which includes DiGeorge (DG) and Velocardiofacial (VCF) syndromes. The aim of the present study is to characterize the phenotype of DG and VCF using facial biometry in 12 portuguese patients. We found 4/12 patients with the DG phenotype: 3/4 had telecanthus, small mouth and retrognathia; 1/4 had telecanthus, short nose with bulbous tip and a normal mouth. These patients had major cardiac defects associated with hypoplastic or absent thymus and monosomy 22q11. We did not find velopharyngeal insufficiency in patients with the so called DG phenotype 8/12 patients had the VCF phenotype: typical facies with variable features. Four of these had velopharyngeal insufficiency and learning disabilities. Four patients had cardiac defects and 5/8 had monosomy 22q11. Probably this clinical variability is due to mutations in critical genes involved in embryonic development.