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Medicina (B Aires),
2009]
Green fluorescent protein (GFP) is a protein produced by the jellyfish Aequorea victoria, that emits bioluminescence in the green zone of the visible spectrum. The GFP gene has been cloned and is used in molecular biology as a marker. The three researchers that participated independently in elucidating the structure and function of this and its related proteins, Drs. Shimomura, Chalfie and Tsien were awarded the Nobel Prize in Chemistry 2008. Dr. Shimomura discovered and studied the properties of GFP. Using molecular biological techniques, Chalfie succeeded in introducing the GFP gene into the DNA of the small, almost transparent worm C. elegans, and initiated an era in which GFP would be used as a glowing marker for cellular biology. Finally, Dr.Tsien found precisely how GFP's structure produces the observed green fluorescence, and succeeded in modifying the structure to generate molecules that emit light at slightly different wavelengths, which gave tags of different colors. Fluorescent proteins are very versatile and are being used in many areas, such as microbiology, biotechnology, physiology, environmental engineering, development, etc. They can, for example, illuminate growing cancer tumours; show the development of Alzheimer's disease, or detect arsenic traces in water. Finding the key to how a marine organism produces light unexpectedly ended up providing researchers with a powerful array of tools with which to visualize cell biology in action.
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Epigenetics,
2009]
Distinct chromatin remodeling complexes can share a common ATPase subunit. The functional characteristics of each remodeling complex are determined by the respective ATPase-associated subunits. The Mi-2 nucleosome remodeling ATPase has so far only been shown to reside within Nucleosome Remodeling and Deacetylase (NuRD) complexes. Here we will review the recent discovery of two Mi-2 related remodelers that function independently of NuRD and that act as SUMO (small ubiquitin-related modifier)-dependent corepressors: First, Mi-2 exists in a novel chromatin remodeling complex, dMec, that does not rely on histone deacetylation to effect transcriptional repression of proneural genes. Second, the Mi-2 related factor dCHD3 acts as a monomer and does not associate with additional subunits in vivo. These recent results have uncovered an unanticipated complexity in the composition and function of CHD (Chromodomain-Helicase-DNA-binding) complexes.
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Front Aging,
2022]
Discoveries made in the nematode Caenorhabditis elegans revealed that aging is under genetic control. Since these transformative initial studies, C. elegans has become a premier model system for aging research. Critically, the genes, pathways, and processes that have fundamental roles in organismal aging are deeply conserved throughout evolution. This conservation has led to a wealth of knowledge regarding both the processes that influence aging and the identification of molecular and cellular hallmarks that play a causative role in the physiological decline of organisms. One key feature of age-associated decline is the failure of mechanisms that maintain proper function of the proteome (proteostasis). Here we highlight components of the proteostatic network that act to maintain the proteome and how this network integrates into major longevity signaling pathways. We focus in depth on the heat shock transcription factor 1 (HSF1), the central regulator of gene expression for proteins that maintain the cytosolic and nuclear proteomes, and a key effector of longevity signals.
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Exp Gerontol,
2012]
Aging represents a triple threat for myocardial infarction (MI). Not only does the incidence of MI increase with age, but the heart becomes more susceptible to MI induced damage and protective interventions such as ischemic preconditioning (IPC) become less effective. Therefore, any rational therapeutic strategy must be built around the ability to combat the detrimental effects of ischemia in aged individuals. To accomplish this, we need to develop a better understanding of how ischemic damage, protection, and aging are linked. In this regard, mitochondria have emerged as a common theme. First, mitochondria contribute to cell damage during ischemia-reperfusion (IR) and are central to cell death. Second, the protective signaling pathways activated by IPC converge on mitochondria, and the opening of mitochondrial ion channels alone is sufficient to elicit protection. Finally, mitochondria clearly influence the aging process, and specific defects in mitochondrial activity are associated with age-related functional decline. This review will summarize the effects of aging on myocardial IR injury and discuss relevant and emerging strategies to protect against MI with an emphasis on mitochondrial function.
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Curr Opin Genet Dev,
2007]
The patterning and development of multicellular organisms require a precisely controlled balance between cell proliferation, differentiation and death. The regulation of apoptosis is an important aspect to achieve this balance, by eliminating unnecessary or mis-specified cells which, otherwise, may have harmful effects on the whole organism. Apoptosis is also important for the morphogenetic processes that occur during development and that lead to the sculpting of organs and other body structures. Here, we review recent progress in understanding how apoptosis is regulated during development, focusing on studies using Drosophila or Caenorhabditis elegans as model organisms.
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Curr Opin Genet Dev,
2012]
The identity of individual cell types in a multicellular organism appears to be continuously maintained through active processes but is not irreversible. Changes in the identity of individual cell types can be brought about through ectopic mis-expression of regulatory factors, but in a number of cases also occurs in normal development. I will review here these natural cellular reprogramming processes occurring in the invertebrate model organisms Caenorhabditis elegans and Drosophila melanogaster. Furthermore, I will discuss the issue of why only certain cell types can be converted during induced reprogramming processes evoked by ectopic expression of regulatory factors and how recent work in model systems have shown that this cellular context-dependency can be manipulated.
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Curr Top Microbiol Immunol,
2003]
ATP-dependent nucleosome remodeling and core histone tail modifications play important roles in chromatin function. Purification and characterization of the NuRD/Mi-2 complex, which possesses both nucleosome remodeling and histone deacetylase activities, suggests that ATP-dependent nucleosome remodeling and histone tail modification can be coupled. Recent studies indicate that NuRD is an integral part of the MeCP1 complex, suggesting that nucleosome remodeling and histone deacetylation play important roles in methylated DNA silencing. Studies in Caenorhabditis elegans have revealed important functions of the NuRD complex in embryonic patterning and Ras signaling. Accumulating evidence indicates that NuRD may regulate transcription of specific genes by interacting with specific transcriptional factors. In addition, it may also participate in genome-wide transcriptional regulation through an association with histone tails.
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Int J Mol Sci,
2015]
Mitochondrial unfolded protein response is a form of retrograde signaling that contributes to ensuring the maintenance of quality control of mitochondria, allowing functional integrity of the mitochondrial proteome. When misfolded proteins or unassembled complexes accumulate beyond the folding capacity, it leads to alteration of proteostasis, damages, and organelle/cell dysfunction. Extensively studied for the ER, it was recently reported that this kind of signaling for mitochondrion would also be able to communicate with the nucleus in response to impaired proteostasis. The mitochondrial unfolded protein response (UPR(mt)) is activated in response to different types and levels of stress, especially in conditions where unfolded or misfolded mitochondrial proteins accumulate and aggregate. A specific UPR(mt) could thus be initiated to boost folding and degradation capacity in response to unfolded and aggregated protein accumulation. Although first described in mammals, the UPR(mt) was mainly studied in Caenorhabditis elegans, and accumulating evidence suggests that mechanisms triggered in response to a UPR(mt) might be different in C. elegans and mammals. In this review, we discuss and integrate recent data from the literature to address whether the UPR(mt) is relevant to mitochondrial homeostasis in mammals and to analyze the putative role of integrated stress response (ISR) activation in response to the inhibition of mtDNA expression and/or accumulation of mitochondrial mis/unfolded proteins.
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Science,
1995]
In many species, females possess two X chromosomes and males have one X chromosome. This difference is critical for the initial determination of sex. However, the X encodes many functions required equally in males and females; thus, X chromosome expression must be adjusted to compensate for the difference in dosage between the sexes. Distinct dosage compensation mechanisms have evolved in different species. A common theme in the Drosophila melanogaster and Caenorhabditis elegans systems is that a subtle alteration of chromatin structure may impose this modest, but vital adjustment of the X chromosome
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Yeast,
2000]
The availability of complete genome sequences necessitates the development of standardized functional assays to analyse the tens of thousands of predicted gene products in high-throughput experimental settings. Such approaches are collectively referred to as 'functional genomics'. One approach to investigate the properties of a proteome of interest is by systematic analysis of protein-protein interactions. So far, the yeast two-hybrid system is the most commonly used method for large-scale, high-throughput identification of potential protein-protein interactions. Here, we discuss several technical features of variants of the two-hybrid systems in light of data recently obtained from different protein interaction mapping projects for the budding yeast Saccharomyces cerevisiae and the nematode Caenorhabditis elegans.