Animal HECT ubiquitin ligases: evolution and functional implications

<p>Abstract</p> <p>Background</p> <p>HECT ubiquitin ligases (HECT E3s) are key components of the eukaryotic ubiquitin-proteasome system and are involved in the genesis of several human diseases. In this study, I analyze the patterns of diversification of HECT E3s since animals emerged in order to provide the right framework to understand the functional data available for proteins of this family.</p> <p>Results</p> <p>I show that the current classification of HECT E3s into three groups (NEDD4-like E3s, HERCs and single-HECT E3s) is fundamentally incorrect. First, the existence of a "Single-HECT E3s" group is not supported by phylogenetic analyses. Second, the HERC proteins must be divided into two subfamilies (Large HERCs, Small HERCs) that are evolutionarily very distant, their structural similarity being due to convergence and not to a common origin. Sequence and structural analyses show that animal HECT E3s can be naturally classified into 16 subfamilies. Almost all of them appeared either before animals originated or in early animal evolution. More recently, multiple gene losses have occurred independently in some lineages (nematodes, insects, urochordates), the same groups that have also lost genes of another type of E3s (RBR family). Interestingly, the emergence of some animal HECT E3s precedes the origin of key cellular systems that they regulate (TGF-β and EGF signal transduction pathways; p53 family of transcription factors) and it can be deduced that distantly related HECT proteins have been independently co-opted to perform similar roles. This may contribute to explain why distantly related HECT E3s are involved in the genesis of multiple types of cancer.</p> <p>Conclusions</p> <p>The complex evolutionary history of HECT ubiquitin ligases in animals has been deciphered. The most appropriate model animals to study them and new theoretical and experimental lines of research are suggested by these results.</p

Diversification of the cullin family

<p>Abstract</p> <p>Background</p> <p>Cullins are proteins involved in ubiquitination through their participation in multisubunit ubiquitin ligase complexes. In this study, I use comparative genomic data to establish the pattern of emergence and diversification of cullins in eukaryotes.</p> <p>Results</p> <p>The available data indicate that there were three cullin genes before the unikont/bikont split, which I have called <it>Culα</it>, <it>Culβ </it>and <it>Culγ</it>. Fungal species have quite strictly conserved these three ancestral genes, with only occasional lineage-specific duplications. On the contrary, several additional genes appeared in the animal or plant lineages. For example, the human genes <it>Cul1</it>, <it>Cul2</it>, <it>Cul5</it>, <it>Cul7 </it>and <it>Parc </it>all derive from the ancestral <it>Culα </it>gene. These results, together with the available functional data, suggest that three different types of ubiquitin ligase cullin-containing complexes were already present in early eukaryotic evolution: 1) SCF-like complexes with Culα proteins; 2) Culβ/BTB complexes; and, 3) Complexes containing Culγ and DDB1-like proteins. Complexes containing elongins have arisen more recently and perhaps twice independently in animals and fungi.</p> <p>Conclusion</p> <p>Most of the known types of cullin-containing ubiquitin ligase complexes are ancient. The available data suggest that, since the origin of eukaryotes, complex diversity has been mostly generated by combining closely related subunits, while radical innovations, giving rise to novel types of complexes, have been scarce. However, several protist groups not examined so far contain highly divergent cullins, indicating that additional types of complexes may exist.</p

Ancient origin of animal U-box ubiquitin ligases

<p>Abstract</p> <p>Background</p> <p>The patterns of emergence and diversification of the families of ubiquitin ligases provide insights about the evolution of the eukaryotic ubiquitination system. U-box ubiquitin ligases (UULs) are proteins characterized by containing a peculiar protein domain known as U box. In this study, the origin of the animal UUL genes is described.</p> <p>Results</p> <p>Phylogenetic and structural data indicate that six of the seven main UUL-encoding genes found in humans (<it>UBE4A</it>, <it>UBE4B</it>, <it>UIP5</it>, <it>PRP19</it>, <it>CHIP </it>and <it>CYC4</it>) were already present in the ancestor of all current metazoans and the seventh (<it>WDSUB1</it>) is found in placozoans, cnidarians and bilaterians. The fact that only 4 - 5 genes orthologous to the human ones are present in the choanoflagellate <it>Monosiga brevicollis </it>suggests that several animal-specific cooptions of the U box to generate new genes occurred. Significantly, <it>Monosiga </it>contains five additional UUL genes that are not present in animals. One of them is also present in distantly-related protozoans. Along animal evolution, losses of UUL-encoding genes are rare, except in nematodes, which lack three of them. These general patterns are highly congruent with those found for other two families (RBR, HECT) of ubiquitin ligases.</p> <p>Conclusions</p> <p>Finding that the patterns of emergence, diversification and loss of three unrelated families of ubiquitin ligases (RBR, HECT and U-box) are parallel indicates that there are underlying, linage-specific evolutionary forces shaping the complexity of the animal ubiquitin system.</p

A general strategy to determine the congruence between a hierarchical and a non-hierarchical classification

This article is available from: http://www.biomedcentral.com/1471-2105/8/442[Background] Classification procedures are widely used in phylogenetic inference, the analysis of expression profiles, the study of biological networks, etc. Many algorithms have been proposed to establish the similarity between two different classifications of the same elements. However, methods to determine significant coincidences between hierarchical and non-hierarchical partitions are still poorly developed, in spite of the fact that the search for such coincidences is implicit in many analyses of massive data.[Results] We describe a novel strategy to compare a hierarchical and a dichotomic non-hierarchical classification of elements, in order to find clusters in a hierarchical tree in which elements of a given "flat" partition are overrepresented. The key improvement of our strategy respect to previous methods is using permutation analyses of ranked clusters to determine whether regions of the dendrograms present a significant enrichment. We show that this method is more sensitive than previously developed strategies and how it can be applied to several real cases, including microarray and interactome data. Particularly, we use it to compare a hierarchical representation of the yeast mitochondrial interactome and a catalogue of known mitochondrial protein complexes, demonstrating a high level of congruence between those two classifications. We also discuss extensions of this method to other cases which are conceptually related.[Conclusion] Our method is highly sensitive and outperforms previously described strategies. A PERL script that implements it is available at http://www.uv.es/~genomica/treetracker.Our group is supported by Grant SAF2006-08977 (Ministerio de Educación y Ciencia [MEC], Spain). A.M. was the recipient of a predoctoral fellowship from the MEC.Peer reviewe

A characterization of some families of Cohen--Macaulay, Gorenstein and/or Buchsbaum rings

We provide algorithmic methods to check the Cohen--Macaulayness, Buchsbaumness and/or Gorensteiness of some families of semigroup rings that are constructed from the dilation of bounded convex polyhedrons of $\R^3_{\geq}$. Some families of semigroup rings are given satifying these properties

Plan de Gestión para la Ejecución de Proyectos de Vivienda de la empresa Servicios Técnicos para la Construcción Quepos S.A.

Proyecto de Graduación (Licenciatura en Ingeniería en Construcción) Instituto Tecnológico de Costa Rica, Escuela de Ingeniería en Construcción, 2014.El presente proyecto abarca la realización de un manual de gestión en las áreas de integración, alcance, costo, tiempo y adquisiciones para la empresa Servicios Técnicos de la Construcción S. A. Como base del proyecto se tomó de referencia y guía, los libros de administración de proyectos: Administración Profesional de Proyectos, La Guía del autor Yamal Chamoun y las técnicas aplicadas basadas en la Guía de los Fundamentos para la Dirección de Proyectos (Guía Del PMBOK®). Se realizó un análisis del estado actual de la empresa, se identificaron los procesos con que cuenta y se optó desarrollar la guía desde cero, debido a que los procesos de la empresa no contaban con una metodología uniforme. Las herramientas generadas en la guía de gestión conceden al equipo de ingeniería la capacidad de iniciar, planear, ejecutar, controlar y cerrar una construcción de una vivienda de dos niveles a partir de los estándares establecidos por el PMI. Se recomienda a la hora de implementar la guía de gestión dentro de la empresa consultar con expertos en la administración de proyectos enfocados en la construcción, la forma más óptima de realizarla.Instituto Tecnológico de Costa Rica: Escuela de Ingeniería en Construcción; Servicios Técnicos para la Construcción Quepos S.A

Programación de la secuencia de fabricación en una máquina, con tiempos de preparación variables, mediante la aplicación de Algoritmos Genéticos

Este proyecto tiene como objetivo minimizar los retrasos que se producen en un problema de secuenciación. El problema se caracteriza, por un lado, porque se dispone de una sola máquina que requiere de unos tiempos de preparación entre la ejecución de diferentes tipos de piezas. La existencia de estos tiempos de preparación aumentan considerablemente el tiempo de producción en la máquina, por lo que interesa evitarlos, haciendo que las ejecuciones de lotes de una misma pieza sean consecutivas. Por otro lado, existe un carné de pedidos cuyas fechas de vencimiento determinan la presencia de retrasos en las entregas. Para un problema como éste, alcanzar la solución óptima requiere un proceso excesivamente largo. Por ello, se recurre al uso de meta-heurísticas, que, aunque no garantizan encontrar la solución óptima, sí son capaces de hallar una solución satisfactoria en un período de tiempo aceptable. La meta-heurística que se ha escogido son los algoritmos genéticos (Genetic Algorithms). Son una técnica de computación evolutiva, común en la resolución de problemas de optimización, cuyo proceso está basado en las ideas de la evolución natural. Cada uno de los diferentes operadores que configuran los algoritmos genéticos ha sido adaptado al problema, mediante la realización de un programa formalizado con la herramienta informática Visual Basic y que recibe el nombre el nombre de “Secuencia de Fabricación”. Los resultados computacionales obtenidos demuestran que el algoritmo genético propuesto logra explorar el espacio de búsqueda de forma eficaz, acortando los tiempos de resolución del problema