The Proteomics of N-terminal Methionine Cleavage

Methionine aminopeptidase (MAP) is a ubiquitous, essential enzyme involved in protein N-terminal methionine excision. According to the generally accepted cleavage rules for MAP, this enzyme cleaves all proteins with small side chains on the residue in the second position (P1′), but many exceptions are known. The substrate specificity of Escherichia coli MAP1 was studied in vitro with a large (\u3e120) coherent array of peptides mimicking the natural substrates and kinetically analyzed in detail. Peptides with Val or Thr at P1′ were much less efficiently cleaved than those with Ala, Cys, Gly, Pro, or Ser in this position. Certain residues at P2′, P3′, and P4′ strongly slowed the reaction, and some proteins with Val and Thr at P1′ could not undergo Met cleavage. These in vitro data were fully consistent with data for 862 E. coli proteins with known N-terminal sequences in vivo. The specificity sites were found to be identical to those for the other type of MAPs, MAP2s, and a dedicated prediction tool for Met cleavage is now available. Taking into account the rules of MAP cleavage and leader peptide removal, the N termini of all proteins were predicted from the annotated genome and compared with data obtained in vivo. This analysis showed that proteins displaying N-Met cleavage are overrepresented in vivo. We conclude that protein secretion involving leader peptide cleavage is more frequent than generally thought

El cardo, el ave y la verdad. Entrevista con el pintor Antonio López

Antonio López es reconocido como uno de los más grandes pintores actuales por numerosas instituciones y por un público muy amplio. Al escoger pintar su entorno más cercano, de manera realista y sin imponer siquiera un estilo, supo que su camino sería difícil y solitario, lejos de los críticos de arte, curadores, galeristas y otros actores de la escena contemporánea. De la fidelidad de su mirada nació una obra, y de esta obra nació el pintor, que nos habla en esta entrevista, al horizonte de una verdad. Entre otros reconocimientos Antonio López recibió el Premio Príncipe de Asturias de las Artes en 1985 y el Premio Velázquez de Artes Plásticas en 2006.Antonio Lopez is recognized as one of today's greatest painters for many institutions and by a wide audience. When choosing paint their immediate environment, realistically and without even impose a style, he learned that his path would be difficult and lonely, far from art critics, curators, gallery owners and other actors of the contemporary scene. The fidelity of his eyes was born a work, and this work the painter, who tells us in this interview, the horizon of a truth born. Among other accolades Antonio Lopez received the Prince of Asturias Award for the Arts in 1985 and the Velázquez Visual Arts Prize in 2006.Antonio Lopez est reconnu comme l'un des plus grands peintres d'aujourd'hui pour de nombreuses institutions et par un large public. Lors du choix de peindre leur environnement immédiat, de façon réaliste et sans même imposer un style, il a appris que son chemin serait difficile et solitaire, loin des critiques d'art, conservateurs, galeristes et autres acteurs de la scène contemporaine. La fidélité de ses yeux est né d'un travail, et ce travail du peintre, qui nous dit dans cette interview, l'horizon d'une vérité né. Parmi les autres récompenses Antonio Lopez a reçu le Prix Prince des Asturies des Arts en 1985 et le Prix des arts visuels Velázquez en 2006

Eutherian mammals use diverse strategies to initiate X-chromosome inactivation during development

 X-chromosome inactivation (XCI) in female mammals allows dosage compensation for X-linked gene products between the sexes1. The developmental regulation of this process has been extensively investigated in mice, where the X chromosome of paternal origin (Xp) is silenced during early embryogenesis owing to imprinted expression of the regulatory RNA, Xist (X-inactive specific transcript). Paternal XCI is reversed in the inner cell mass of the blastocyst and random XCI subsequently occurs in epiblast cells. Here we show that other eutherian mammals have very different strategies for initiating XCI. In rabbits and humans, the Xist homologue is not subject to imprinting and XCI begins later than in mice. Furthermore,Xist is upregulated on both X chromosomes in a high proportion of rabbit andhuman embryo cells, even in the inner cell mass. In rabbits, this triggers XCI on both X chromosomes in some cells. In humans, chromosome-wide XCI has not initiated even by the blastocyst stage, despite the upregulation of XIST. The choice of which X chromosome will finally become inactive thus occurs downstream of Xist upregulation in both rabbits and humans, unlike in mice. Our study demonstrates the remarkable diversity in XCI regulation and highlights differences between mammals in their requirement for dosage compensation during early embryogenesis