Publication List

@article{Salichs2009,
title = {Genome-wide analysis of histidine repeats reveals their role in the localization of human proteins to the nuclear speckles compartment.},
author = {Salichs, Eulàlia and Ledda, Alice and Mularoni, Loris and Albà, M Mar and de la Luna, Susana},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2644819&tool=pmcentrez&rendertype=abstract},
issn = {1553-7404},
year = {2009},
date = {2009-01-01},
journal = {PLoS genetics},
volume = {5},
number = {3},
pages = {e1000397},
abstract = {Single amino acid repeats are prevalent in eukaryote organisms, although the role of many such sequences is still poorly understood. We have performed a comprehensive analysis of the proteins containing homopolymeric histidine tracts in the human genome and identified 86 human proteins that contain stretches of five or more histidines. Most of them are endowed with DNA- and RNA-related functions, and, in addition, there is an overrepresentation of proteins expressed in the brain and/or nervous system development. An analysis of their subcellular localization shows that 15 of the 22 nuclear proteins identified accumulate in the nuclear subcompartment known as nuclear speckles. This localization is lost when the histidine repeat is deleted, and significantly, closely related paralogous proteins without histidine repeats also fail to localize to nuclear speckles. Hence, the histidine tract appears to be directly involved in targeting proteins to this compartment. The removal of DNA-binding domains or treatment with RNA polymerase II inhibitors induces the re-localization of several polyhistidine-containing proteins from the nucleoplasm to nuclear speckles. These findings highlight the dynamic relationship between sites of transcription and nuclear speckles. Therefore, we define the histidine repeats as a novel targeting signal for nuclear speckles, and we suggest that these repeats are a way of generating evolutionary diversification in gene duplicates. These data contribute to our better understanding of the physiological role of single amino acid repeats in proteins.},
keywords = {Amino Acids, Cell Line, Cell Nucleus, Cell Nucleus: chemistry, Cell Nucleus: genetics, Cell Nucleus: metabolism, Genome, Histidine, Histidine: chemistry, Histidine: genetics, Histidine: metabolism, human, Humans, Molecular Sequence Data, Nuclear Localization Signals, Nuclear Proteins, Nuclear Proteins: chemistry, Nuclear Proteins: genetics, Nuclear Proteins: metabolism, Protein Transport, Proteins, Proteins: chemistry, Proteins: genetics, Proteins: metabolism, Sequence Alignment, Tandem Repeat Sequences}
}

@article{Rodilla2009,
title = {Jagged1 is the pathological link between Wnt and Notch pathways in colorectal cancer.},
author = {Rodilla, Verónica and Villanueva, Alberto and Obrador-Hevia, Antonia and Robert-Moreno, Alex and Fernández-Majada, Vanessa and Grilli, Andrea and López-Bigas, Nuria and Bellora, Nicolás and Albà, M Mar and Torres, Ferran and Duñach, Mireia and Sanjuan, Xavier and Gonzalez, Sara and Gridley, Thomas and Capella, Gabriel and Bigas, Anna and Espinosa, Lluís},
url = {http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2669348&tool=pmcentrez&rendertype=abstract},
issn = {1091-6490},
year = {2009},
date = {2009-01-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {106},
number = {15},
pages = {6315--20},
abstract = {Notch has been linked to beta-catenin-dependent tumorigenesis; however, the mechanisms leading to Notch activation and the contribution of the Notch pathway to colorectal cancer is not yet understood. By microarray analysis, we have identified a group of genes downstream of Wnt/beta-catenin (down-regulated when blocking Wnt/beta-catenin) that are directly regulated by Notch (repressed by gamma-secretase inhibitors and up-regulated by active Notch1 in the absence of beta-catenin signaling). We demonstrate that Notch is downstream of Wnt in colorectal cancer cells through beta-catenin-mediated transcriptional activation of the Notch-ligand Jagged1. Consistently, expression of activated Notch1 partially reverts the effects of blocking Wnt/beta-catenin pathway in tumors implanted s.c. in nude mice. Crossing APC(Min/+) with Jagged1(+/Delta) mice is sufficient to significantly reduce the size of the polyps arising in the APC mutant background indicating that Notch is an essential modulator of tumorigenesis induced by nuclear beta-catenin. We show that this mechanism is operating in human tumors from Familial Adenomatous Polyposis patients. We conclude that Notch activation, accomplished by beta-catenin-mediated up-regulation of Jagged1, is required for tumorigenesis in the intestine. The Notch-specific genetic signature is sufficient to block differentiation and promote vasculogenesis in tumors whereas proliferation depends on both pathways.},
keywords = {Alleles, Animals, beta Catenin, beta Catenin: metabolism, Calcium-Binding Proteins, Calcium-Binding Proteins: genetics, Calcium-Binding Proteins: metabolism, Cell Line, Cell Nucleus, Cell Nucleus: metabolism, Colorectal Neoplasms, Colorectal Neoplasms: blood supply, Colorectal Neoplasms: genetics, Colorectal Neoplasms: metabolism, Colorectal Neoplasms: pathology, Gene Expression Profiling, Gene Expression Regulation, Genetic, Genetic: genetics, Humans, Intercellular Signaling Peptides and Proteins, Intercellular Signaling Peptides and Proteins: gen, Intercellular Signaling Peptides and Proteins: met, Membrane Proteins, Membrane Proteins: genetics, Membrane Proteins: metabolism, Mice, Neoplastic, Notch, Notch: metabolism, Receptors, Signal Transduction, TCF Transcription Factors, TCF Transcription Factors: metabolism, Transcription, Transgenic, Wnt Proteins, Wnt Proteins: metabolism}
}