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Search Results: 1 - 10 of 32293 matches for " Peter Marynen "
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Evidence for Co-Evolution between Human MicroRNAs and Alu-Repeats
Stefan Lehnert, Peter Van Loo, Pushpike J. Thilakarathne, Peter Marynen, Geert Verbeke, Frans C. Schuit
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004456
Abstract: This paper connects Alu repeats, the most abundant repetitive elements in the human genome and microRNAs, small RNAs that alter gene expression at the post-transcriptional level. Base-pair complementarity could be demonstrated between the seed sequence of a subset of human microRNAs and Alu repeats that are integrated parallel (sense) in mRNAs. The most common target site coincides with the evolutionary most conserved part of Alu. A primate-specific gene cluster on chromosome 19 encodes the majority of miRNAs that target the most conserved sense Alu site. The individual miRNA genes within this cluster are flanked by an Alu-LINE signature, which has been duplicated with the clustered miRNA genes. Gene duplication events in this locus are supported by comparing repeat length variations of the LINE elements within the cluster with those in the rest of the chromosome. Thus, a dual relationship exists between an evolutionary young miRNA cluster and their Alu targets that may have evolved in the same time window. One hypothesis for this dual relationship is that these miRNAs could protect against too high rates of duplicative transposition, which would destroy the genome.
ModuleMiner - improved computational detection of cis-regulatory modules: are there different modes of gene regulation in embryonic development and adult tissues?
Peter Van Loo, Stein Aerts, Bernard Thienpont, Bart De Moor, Yves Moreau, Peter Marynen
Genome Biology , 2008, DOI: 10.1186/gb-2008-9-4-r66
Abstract: The identification and functional annotation of transcriptional regulatory sequences in the human genome is lagging far behind the rapidly increasing knowledge of protein-encoding genes. These transcriptional regulatory sequences are often build up in a modular manner and exert their function in cis through the concerted binding of multiple transcription factors (and co-factors), resulting in the formation of protein complexes that interact with RNA polymerase II [1,2]. These sequences are called cis-regulatory modules (CRMs). In theory, these CRMs can be detected by the presence of multiple transcription factor binding sites (TFBSs). In practice, however, reliable detection of functional TFBSs is difficult and results in many false positives, partly because these binding sites are too short and too degenerate [3]. Hence, the computational detection of functional regulatory sequences in the human genome remains a formidable challenge.Multiple methods have been developed that aim to detect regulatory sequences computationally [4-8]. Promising and validated results have been delivered mostly in model organisms with relatively compact genomes (for example, Drosophila melanogaster) [9-11]. In the larger human genome, deep sequence conservation (for instance, up to zebrafish) or extreme sequence conservation (for example, perfect conservation in mouse over 200 base pairs), irrespective of TFBS detection, remains the method of choice for approaches validating regulatory sequences in vitro or in vivo [12-14]. Although these conservation approaches are quite successful in predicting which regions have a regulatory function, they provide no information regarding what expression pattern these regions produce and by which transcription factors they are targeted.When several similar CRMs have been characterized, and the regulatory factors and binding sites have been elucidated, one can use this knowledge to find new examples of similar CRMs that direct the transcription of othe
The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila
Wouter Bossuyt,Natalie De Geest,Stein Aerts,Iris Leenaerts,Peter Marynen,Bassem A. Hassan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000040
Abstract: The acquisition of terminal cell fate and onset of differentiation are instructed by cell type–specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
The Dark Side of EGFP: Defective Polyubiquitination
Mathijs Baens, Heidi Noels, Vicky Broeckx, Sofie Hagens, Sabine Fevery, An D. Billiau, Hugo Vankelecom, Peter Marynen
PLOS ONE , 2006, DOI: 10.1371/journal.pone.0000054
Abstract: Enhanced Green Fluorescent Protein (EGFP) is the most commonly used live cell reporter despite a number of conflicting reports that it can affect cell physiology. Thus far, the precise mechanism of GFP-associated defects remained unclear. Here we demonstrate that EGFP and EGFP fusion proteins inhibit polyubiquitination, a posttranslational modification that controls a wide variety of cellular processes, like activation of kinase signalling or protein degradation by the proteasome. As a consequence, the NF-κB and JNK signalling pathways are less responsive to activation, and the stability of the p53 tumour suppressor is enhanced in cell lines and in vivo. In view of the emerging role of polyubiquitination in the regulation of numerous cellular processes, the use of EGFP as a live cell reporter should be carefully considered.
The Atonal Proneural Transcription Factor Links Differentiation and Tumor Formation in Drosophila
Wouter Bossuyt,Natalie De Geest,Stein Aerts,Iris Leenaerts,Peter Marynen,Bassem A Hassan
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000040
Abstract: The acquisition of terminal cell fate and onset of differentiation are instructed by cell type–specific master control genes. Loss of differentiation is frequently observed during cancer progression, but the underlying causes and mechanisms remain poorly understood. We tested the hypothesis that master regulators of differentiation may be key regulators of tumor formation. Using loss- and gain-of-function analyses in Drosophila, we describe a critical anti-oncogenic function for the atonal transcription factor in the fly retina, where atonal instructs tissue differentiation. In the tumor context, atonal acts by regulating cell proliferation and death via the JNK stress response pathway. Combined with evidence that atonal's mammalian homolog, ATOH1, is a tumor suppressor gene, our data support a critical, evolutionarily conserved, function for ato in oncogenesis.
Auto-Ubiquitination-Induced Degradation of MALT1-API2 Prevents BCL10 Destabilization in t(11;18)(q21;q21)-Positive MALT Lymphoma
Heidi Noels, Riet Somers, Hongxiang Liu, Hongtao Ye, Ming-Qing Du, Christiane De Wolf-Peeters, Peter Marynen, Mathijs Baens
PLOS ONE , 2009, DOI: 10.1371/journal.pone.0004822
Abstract: Background The translocation t(11;18)(q21;q21) is the most frequent chromosomal aberration associated with MALT lymphoma and results in constitutive NF-κB activity via the expression of an API2-MALT1 fusion protein. The properties of the reciprocal MALT1-API2 were never investigated as it was reported to be rarely transcribed. Principal Findings Our data indicate the presence of MALT1-API2 transcripts in the majority of t(11;18)(q21;q21)-positive MALT lymphomas. Based on the breakpoints in the MALT1 and API2 gene, the MALT1-API2 protein contains the death domain and one or both immunoglobulin-like domains of MALT1 (~90% of cases) - mediating the possible interaction with BCL10 - fused to the RING domain of API2. Here we show that this RING domain enables MALT1-API2 to function as an E3 ubiquitin ligase for BCL10, inducing its ubiquitination and proteasomal degradation in vitro. Expression of MALT1-API2 transcripts in t(11;18)(q21;q21)-positive MALT lymphomas was however not associated with a reduction of BCL10 protein levels. Conclusion As we observed MALT1-API2 to be an efficient target of its own E3 ubiquitin ligase activity, our data suggest that this inherent instability of MALT1-API2 prevents its accumulation and renders a potential effect on MALT lymphoma development via destabilization of BCL10 unlikely.
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt,Avedis Kazanjian,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P. Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F. Shroyer,Bassem A. Hassan
PLOS Biology , 2012, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
Atonal homolog 1 Is a Tumor Suppressor Gene
Wouter Bossuyt equal contributor,Avedis Kazanjian equal contributor,Natalie De Geest,Sofie Van Kelst,Gert De Hertogh,Karel Geboes,Greg P Boivin,Judith Luciani,Francois Fuks,Marinee Chuah,Thierry VandenDriessche,Peter Marynen,Jan Cools,Noah F Shroyer ,Bassem A Hassan
PLOS Biology , 2009, DOI: 10.1371/journal.pbio.1000039
Abstract: Colon cancer accounts for more than 10% of all cancer deaths annually. Our genetic evidence from Drosophila and previous in vitro studies of mammalian Atonal homolog 1 (Atoh1, also called Math1 or Hath1) suggest an anti-oncogenic function for the Atonal group of proneural basic helix-loop-helix transcription factors. We asked whether mouse Atoh1 and human ATOH1 act as tumor suppressor genes in vivo. Genetic knockouts in mouse and molecular analyses in the mouse and in human cancer cell lines support a tumor suppressor function for ATOH1. ATOH1 antagonizes tumor formation and growth by regulating proliferation and apoptosis, likely via activation of the Jun N-terminal kinase signaling pathway. Furthermore, colorectal cancer and Merkel cell carcinoma patients show genetic and epigenetic ATOH1 loss-of-function mutations. Our data indicate that ATOH1 may be an early target for oncogenic mutations in tissues where it instructs cellular differentiation.
Ubiquitin Ligase HUWE1 Regulates Axon Branching through the Wnt/β-Catenin Pathway in a Drosophila Model for Intellectual Disability
Joke Vandewalle, Marion Langen, Marlen Zschaetzsch, Bonnie Nijhof, Jamie M. Kramer, Hilde Brems, Marijke Bauters, Elsa Lauwers, Mohammed Srahna, Peter Marynen, Patrik Verstreken, Annette Schenck, Bassem A. Hassan, Guy Froyen
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0081791
Abstract: We recently reported that duplication of the E3 ubiquitin ligase HUWE1 results in intellectual disability (ID) in male patients. However, the underlying molecular mechanism remains unknown. We used Drosophila melanogaster as a model to investigate the effect of increased HUWE1 levels on the developing nervous system. Similar to the observed levels in patients we overexpressed the HUWE1 mRNA about 2-fold in the fly. The development of the mushroom body and neuromuscular junctions were not altered, and basal neurotransmission was unaffected. These data are in agreement with normal learning and memory in the courtship conditioning paradigm. However, a disturbed branching phenotype at the axon terminals of the dorsal cluster neurons (DCN) was detected. Interestingly, overexpression of HUWE1 was found to decrease the protein levels of dishevelled (dsh) by 50%. As dsh as well as Fz2 mutant flies showed the same disturbed DCN branching phenotype, and the constitutive active homolog of β-catenin, armadillo, could partially rescue this phenotype, our data strongly suggest that increased dosage of HUWE1 compromises the Wnt/β-catenin pathway possibly by enhancing the degradation of dsh.
Natural Rights, Morality, and the Law  [PDF]
Drum Peter
Beijing Law Review (BLR) , 2011, DOI: 10.4236/blr.2011.21004
Abstract: It is argued that despite attempts to discount the importance of natural rights for morality, they are fundamental to it; therefore, so too are natural rights to the legitimacy of the law.
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