Gene Silencing

Publication Title: 
Journal of Cell Science

In mammalian cells, products of the INK4a-ARF locus play major roles in senescence and tumour suppression in different contexts, whereas the adjacent INK4b gene is more generally associated with transforming growth factor beta (TGF-beta)-mediated growth arrest. As the chicken genome does not encode an equivalent of INK4a, we asked whether INK4b and/or ARF contribute to replicative senescence in chicken cells.

Author(s): 
Kim, Soo-Hyun
Rowe, Janice
Fujii, Hideta
Jones, Rebecca
Schmierer, Bernhard
Kong, Byung-Whi
Kuchler, Karl
Foster, Douglas
Ish-Horowicz, David
Peters, Gordon
Publication Title: 
Journal of Virology

Human papillomaviruses (HPVs) belonging to the Betapapillomavirus genus have recently been implicated in squamous cell carcinomas of the skin, though the mechanisms by which they initiate carcinogenesis are unclear. We show that human foreskin keratinocytes (HFKs) expressing several betapapillomavirus E6 (beta-E6) proteins display life span extension, but not to the extent seen in HFKs expressing HPV type 16 E6 (16E6). Additionally, we demonstrate that beta-E6 proteins can differentially activate telomerase.

Author(s): 
Bedard, Kristin M.
Underbrink, Michael P.
Howie, Heather L.
Galloway, Denise A.
Publication Title: 
Experimental Gerontology

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C.

Author(s): 
Schiavi, Alfonso
Torgovnick, Alessandro
Kell, Alison
Megalou, Evgenia
Castelein, Natascha
Guccini, Ilaria
Marzocchella, Laura
Gelino, Sara
Hansen, Malene
Malisan, Florence
CondÚ, Ivano
Bei, Roberto
Rea, Shane L.
Braeckman, Bart P.
Tavernarakis, Nektarios
Testi, Roberto
Ventura, Natascia
Publication Title: 
Molecular Biology of the Cell

Forkhead box O (FOXO) transcription factors control diverse cellular functions, such as cell death, metabolism, and longevity. We analyzed FOXO3/FKHRL1 expression and subcellular localization in tumor sections of neuroblastoma patients and observed a correlation between nuclear FOXO3 and high caspase-8 expression. In neuroblastoma caspase-8 is frequently silenced by DNA methylation. Conditional FOXO3 activated caspase-8 gene expression but did not change the DNA-methylation pattern of regulatory sequences in the caspase-8 gene.

Author(s): 
Geiger, Kathrin
Hagenbuchner, Judith
Rupp, Martina
Fiegl, Heidi
Sergi, Consolato
Meister, Bernhard
Kiechl-Kohlendorfer, Ursula
M¸ller, Thomas
Ausserlechner, Michael J.
Obexer, Petra
Publication Title: 
Experimental Gerontology

Severe mitochondria deficiency leads to a number of devastating degenerative disorders, yet, mild mitochondrial dysfunction in different species, including the nematode Caenorhabditis elegans, can have pro-longevity effects. This apparent paradox indicates that cellular adaptation to partial mitochondrial stress can induce beneficial responses, but how this is achieved is largely unknown. Complete absence of frataxin, the mitochondrial protein defective in patients with Friedreich's ataxia, is lethal in C.

Author(s): 
Schiavi, Alfonso
Torgovnick, Alessandro
Kell, Alison
Megalou, Evgenia
Castelein, Natascha
Guccini, Ilaria
Marzocchella, Laura
Gelino, Sara
Hansen, Malene
Malisan, Florence
CondÚ, Ivano
Bei, Roberto
Rea, Shane L.
Braeckman, Bart P.
Tavernarakis, Nektarios
Testi, Roberto
Ventura, Natascia
Publication Title: 
Experimental Cell Research

Soft tissue sarcomas (STS) are characterized by co-participation of several epigenetic and genetic events during tumorigenesis. Having bypassed cellular senescence barriers during oncogenic transformation, the factors further affecting growth rate of STS cells remain poorly understood.

Author(s): 
Becerikli, Mustafa
Jacobsen, Frank
Rittig, Andrea
Kˆhne, Wiebke
Nambiar, Sandeep
Mirmohammadsadegh, Alireza
Stricker, Ingo
Tannapfel, Andrea
Wieczorek, Stefan
Epplen, Joerg Thomas
Tilkorn, Daniel
Steinstraesser, Lars
Publication Title: 
Developmental Cell

Developmental timing genes catalyze stem cell progression and animal maturation programs across taxa. Caenorhabditis elegans DRE-1/FBXO11 functions in an SCF E3-ubiquitin ligase complex to regulate the transition to adult programs, but its cognate proteolytic substrates are unknown. Here, we identify the conserved transcription factor BLMP-1 as a substrate of the SCF(DRE-1/FBXO11) complex. blmp-1 deletion suppressed dre-1 mutant phenotypes and exhibited developmental timing defects opposite to dre-1.

Author(s): 
Horn, Moritz
Geisen, Christoph
Cermak, Lukas
Becker, Ben
Nakamura, Shuhei
Klein, Corinna
Pagano, Michele
Antebi, Adam
Publication Title: 
Nature Reviews. Genetics
Author(s): 
Alfred, J.
Publication Title: 
Genetics

Telomeres are an unusual component of the genome because they do not encode genes, but their structure and cellular maintenance machinery (which we define as "telotype") are essential for chromosome stability. Cells can switch between different phenotypic states. One such example is when they switch from maintenance mediated by telomerase (TERT telotype) to one of the two alternative mechanisms of telomere preservation (ALT I and ALT II telotype). The nature of this switch is largely unknown.

Author(s): 
Makovets, Svetlana
Williams, Tanya L.
Blackburn, Elizabeth H.
Publication Title: 
Journal of Neurology, Neurosurgery, and Psychiatry

OBJECTIVES: Cerebellar haemangioblastoma occurs sporadically or as a component tumour of autosomal dominant von Hippel-Lindau disease. Biallelic inactivation of the VHL tumour suppressor gene, which is located on chromosome 3p, has been shown to be involved in the pathogenesis of both tumour entities. Mechanisms of VHL inactivation are intragenic mutations, mitotic recombination events, and hypermethylation of the promoter region.

Author(s): 
Gl‰sker, S.
Bender, B. U.
Apel, T. W.
van Velthoven, V.
Mulligan, L. M.
Zentner, J.
Neumann, H. P.

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