The Experts below are selected from a list of 12105 Experts worldwide ranked by ideXlab platform
Andrew Garnham - One of the best experts on this subject based on the ideXlab platform.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling following short term concurrent versus single mode resistance training
Scientific Reports, 2018Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew GarnhamAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in Ribosome Biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling with concurrent versus single mode resistance training
bioRxiv, 2017Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew Garnham, Nigel K SteptoAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT performed alone. Twenty-three recreationally-active males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor, and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT alone. However, during the final training session, RT induced further increases in both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT preferentially induces mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in skeletal muscle Ribosome Biogenesis markers were more favourable following concurrent training versus RT performed alone.
Susan J. Baserga - One of the best experts on this subject based on the ideXlab platform.
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MicroRNAs and long non-coding RNAs as novel regulators of Ribosome Biogenesis.
Biochemical Society transactions, 2020Co-Authors: Mason A Mccool, Carson J Bryant, Susan J. BasergaAbstract:Ribosome Biogenesis is the fine-tuned, essential process that generates mature ribosomal subunits and ultimately enables all protein synthesis within a cell. Novel regulators of Ribosome Biogenesis continue to be discovered in higher eukaryotes. While many known regulatory factors are proteins or small nucleolar ribonucleoproteins, microRNAs (miRNAs), and long non-coding RNAs (lncRNAs) are emerging as a novel modulatory layer controlling Ribosome production. Here, we summarize work uncovering non-coding RNAs (ncRNAs) as novel regulators of Ribosome Biogenesis and highlight their links to diseases of defective Ribosome Biogenesis. It is still unclear how many miRNAs or lncRNAs are involved in phenotypic or pathological disease outcomes caused by impaired Ribosome production, as in the ribosomopathies, or by increased Ribosome production, as in cancer. In time, we hypothesize that many more ncRNA regulators of Ribosome Biogenesis will be discovered, which will be followed by an effort to establish connections between disease pathologies and the molecular mechanisms of this additional layer of Ribosome Biogenesis control.
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Fanconi anemia protein FANCI functions in Ribosome Biogenesis.
Proceedings of the National Academy of Sciences of the United States of America, 2019Co-Authors: Samuel B. Sondalle, Lisa M. Ogawa, Simonne Longerich, Patrick Sung, Susan J. BasergaAbstract:Fanconi anemia (FA) is a disease of DNA repair characterized by bone marrow failure and a reduced ability to remove DNA interstrand cross-links. Here, we provide evidence that the FA protein FANCI also functions in Ribosome Biogenesis, the process of making Ribosomes that initiates in the nucleolus. We show that FANCI localizes to the nucleolus and is functionally and physically tied to the transcription of pre-ribosomal RNA (pre-rRNA) and to large ribosomal subunit (LSU) pre-rRNA processing independent of FANCD2. While FANCI is known to be monoubiquitinated when activated for DNA repair, we find that it is predominantly in the deubiquitinated state in the nucleolus, requiring the nucleoplasmic deubiquitinase (DUB) USP1 and the nucleolar DUB USP36. Our model suggests a possible dual pathophysiology for FA that includes defects in DNA repair and in Ribosome Biogenesis.
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Diverse Regulators of Human Ribosome Biogenesis Discovered by Changes in Nucleolar Number
Cell reports, 2018Co-Authors: Katherine I. Farley-barnes, Kathleen L. Mccann, Lisa M. Ogawa, Janie Merkel, Yulia V. Surovtseva, Susan J. BasergaAbstract:Ribosome Biogenesis is a highly regulated, essential cellular process. Although studies in yeast have established some of the biological principles of Ribosome Biogenesis, many of the intricacies of its regulation in higher eukaryotes remain unknown. To understand how Ribosome Biogenesis is globally integrated in human cells, we conducted a genome-wide siRNA screen for regulators of nucleolar number. We found 139 proteins whose depletion changed the number of nucleoli per nucleus from 2-3 to only 1 in human MCF10A cells. Follow-up analyses on 20 hits found many (90%) to be essential for the nucleolar functions of rDNA transcription (7), pre-ribosomal RNA (pre-rRNA) processing (16), and/or global protein synthesis (14). This genome-wide analysis exploits the relationship between nucleolar number and function to discover diverse cellular pathways that regulate the making of Ribosomes and paves the way for further exploration of the links between Ribosome Biogenesis and human disease.
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Tissue Specific Roles for the Ribosome Biogenesis Factor Wdr43 in Zebrafish Development
PLoS genetics, 2014Co-Authors: Chengtian Zhao, Kathleen L. Mccann, Viktoria Andreeva, Yann Gibert, Melissa Labonty, Victoria J. Lattanzi, Shubhangi Prabhudesai, Yi Zhou, Leonard I. Zon, Susan J. BasergaAbstract:During vertebrate craniofacial development, neural crest cells (NCCs) contribute to most of the craniofacial pharyngeal skeleton. Defects in NCC specification, migration and differentiation resulting in malformations in the craniofacial complex are associated with human craniofacial disorders including Treacher-Collins Syndrome, caused by mutations in TCOF1. It has been hypothesized that perturbed Ribosome Biogenesis and resulting p53 mediated neuroepithelial apoptosis results in NCC hypoplasia in mouse Tcof1 mutants. However, the underlying mechanisms linking Ribosome Biogenesis and NCC development remain poorly understood. Here we report a new zebrafish mutant, fantome (fan), which harbors a point mutation and predicted premature stop codon in zebrafish wdr43, the ortholog to yeast UTP5. Although wdr43 mRNA is widely expressed during early zebrafish development, and its deficiency triggers early neural, eye, heart and pharyngeal arch defects, later defects appear fairly restricted to NCC derived craniofacial cartilages. Here we show that the C-terminus of Wdr43, which is absent in fan mutant protein, is both necessary and sufficient to mediate its nucleolar localization and protein interactions in metazoans. We demonstrate that Wdr43 functions in Ribosome Biogenesis, and that defects observed in fan mutants are mediated by a p53 dependent pathway. Finally, we show that proper localization of a variety of nucleolar proteins, including TCOF1, is dependent on that of WDR43. Together, our findings provide new insight into roles for Wdr43 in development, Ribosome Biogenesis, and also ribosomopathy-induced craniofacial phenotypes including Treacher-Collins Syndrome.
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When Ribosomes go bad: diseases of Ribosome Biogenesis
Molecular bioSystems, 2010Co-Authors: Emily F. Freed, Franziska Bleichert, Laura M. Dutca, Susan J. BasergaAbstract:Ribosomes are vital for cell growth and survival. Until recently, it was believed that mutations in Ribosomes or Ribosome Biogenesis factors would be lethal, due to the essential nature of these complexes. However, in the last few decades, a number of diseases of Ribosome Biogenesis have been discovered. It remains a challenge in the field to elucidate the molecular mechanisms underlying them.
Jackson J Fyfe - One of the best experts on this subject based on the ideXlab platform.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling following short term concurrent versus single mode resistance training
Scientific Reports, 2018Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew GarnhamAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in Ribosome Biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling with concurrent versus single mode resistance training
bioRxiv, 2017Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew Garnham, Nigel K SteptoAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT performed alone. Twenty-three recreationally-active males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor, and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT alone. However, during the final training session, RT induced further increases in both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT preferentially induces mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in skeletal muscle Ribosome Biogenesis markers were more favourable following concurrent training versus RT performed alone.
Massimo Derenzini - One of the best experts on this subject based on the ideXlab platform.
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The Ribosome Biogenesis-Cancer Connection.
Cells, 2019Co-Authors: Marianna Penzo, Davide Treré, Lorenzo Montanaro, Massimo DerenziniAbstract:Multifaceted relations link Ribosome Biogenesis to cancer. Ribosome Biogenesis takes place in the nucleolus. Clarifying the mechanisms involved in this nucleolar function and its relationship with cell proliferation: (1) allowed the understanding of the reasons for the nucleolar changes in cancer cells and their exploitation in tumor pathology, (2) defined the importance of the inhibition of Ribosome Biogenesis in cancer chemotherapy and (3) focused the attention on alterations of Ribosome Biogenesis in the pathogenesis of cancer. This review summarizes the research milestones regarding these relevant relationships between Ribosome Biogenesis and cancer. The structure and function of the nucleolus will also be briefly described.
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Ribosome Biogenesis and cancer.
Acta Histochemica, 2017Co-Authors: Massimo Derenzini, Lorenzo Montanaro, Davide TreréAbstract:Abstract There is growing evidence indicating that the human pathological conditions characterized by an up-regulated Ribosome Biogenesis are at an increased risk of cancer onset. At the basis of this relationship is the close interconnection between the Ribosome Biogenesis and cell proliferation. Cell proliferation-stimulating factors also stimulate Ribosome production, while the Ribosome Biogenesis rate controls the cell cycle progression. The major tumour suppressor, the p53 protein, plays an important balancing role between the Ribosome Biogenesis rate and the cell progression through the cell cycle phases. The perturbation of Ribosome Biogenesis stabilizes and activates p53, with a consequent cell cycle arrest and/or apoptotic cell death, whereas an up-regulated Ribosome production down-regulates p53 expression and activity, thus facilitating neoplastic transformation. In the present review we describe the interconnection between Ribosome Biogenesis and cell proliferation, while highlighting the mechanisms by which quantitative changes in Ribosome Biogenesis may induce cancer.
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Direct relationship between the level of p53 stabilization induced by rRNA synthesis-inhibiting drugs and the cell Ribosome Biogenesis rate
Oncogene, 2016Co-Authors: F Scala, Davide Treré, E Brighenti, M Govoni, E Imbrogno, F Fornari, L Montanaro, Massimo DerenziniAbstract:Many drugs currently used in chemotherapy work by hindering the process of Ribosome Biogenesis. In tumors with functional p53, the inhibition of Ribosome Biogenesis may contribute to the efficacy of this treatment by inducing p53 stabilization. As the level of stabilized p53 is critical for the induction of cytotoxic effects, it seems useful to highlight those cancer cell characteristics that can predict the degree of p53 stabilization following the treatment with inhibitors of Ribosome Biogenesis. In the present study we exposed a series of p53 wild-type human cancer cell lines to drugs such as actinomycin D (ActD), doxorubicin, 5-fluorouracil and CX-5461, which hinder ribosomal RNA (rRNA) synthesis. We found that the amount of stabilized p53 was directly related to the level of Ribosome Biogenesis in cells before the drug treatment. This was due to different levels of inactivation of the ribosomal proteins–MDM2 pathway of p53 digestion. Inhibition of rRNA synthesis always caused cell cycle arrest, independent of the Ribosome Biogenesis rate of the cells, whereas apoptosis occurred only in cells with a high rDNA transcription rate. The level of p53 stabilization induced by drugs acting in different ways from the inhibition of Ribosome Biogenesis, such as hydroxyurea (HU) and nutlin-3, was independent of the level of Ribosome Biogenesis in cells and always lower than that occurring after the inhibition of rRNA synthesis. Interestingly, in cells with a low Ribosome Biogenesis rate, the combined treatment with ActD and HU exerted an additive effect on p53 stabilization. These results indicated that (i) drugs inhibiting Ribosome Biogenesis may be highly effective in p53 wild-type cancers with a high Ribosome Biogenesis rate, as they induce apoptotic cell death, and (ii) the combination of drugs capable of stabilizing p53 through different mechanisms may be useful for treating cancers with a low Ribosome Biogenesis rate.
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Targeted cancer therapy with Ribosome Biogenesis inhibitors: a real possibility?
Oncotarget, 2015Co-Authors: Elisa Brighenti, Davide Treré, Massimo DerenziniAbstract:The effects of many chemotherapeutic drugs on Ribosome Biogenesis have been underestimated for a long time. Indeed, many drugs currently used for cancer treatment--and which are known to either damage DNA or hinder DNA synthesis--have been shown to exert their toxic action mainly by inhibiting rRNA synthesis or maturation. Moreover, there are new drugs that have been proposed recently for cancer chemotherapy, which only hinder Ribosome Biogenesis without any genotoxic activity. Even though Ribosome Biogenesis occurs in both normal and cancer cells, whether resting or proliferating, there is evidence that the selective inhibition of Ribosome Biogenesis may, in some instances, result in a selective damage to neoplastic cells. The higher sensitivity of cancer cells to inhibitors of rRNA synthesis appears to be the consequence of either the loss of the mechanisms controlling the cell cycle progression or the acquisition of activating oncogene and inactivating tumor suppressor gene mutations that up-regulate the Ribosome Biogenesis rate. This article reviews those cancer cell characteristics on which the selective cancer cell cytotoxicity induced by the inhibitors of Ribosome Biogenesis is based.
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Ribosome Biogenesis and Control of Cell Proliferation: p53 Is Not Alone
Cancer research, 2012Co-Authors: Giulio Donati, Lorenzo Montanaro, Massimo DerenziniAbstract:Cell growth is a prerequisite for cell proliferation, and Ribosome Biogenesis is a limiting factor for cell growth. In mammalian cells, the tumor suppressor p53 has been shown to induce cell-cycle arrest in response to impaired Ribosome Biogenesis. Recently, p53-independent mechanisms of cell-cycle arrest in response to alterations of Ribosome Biogenesis have been described. These findings provide a rational basis for the use of drugs that specifically impact Ribosome Biogenesis for the treatment of cancers lacking active p53 and extend the scenario of mechanisms involved in the relationship between cell growth and cell proliferation.
David Bishop - One of the best experts on this subject based on the ideXlab platform.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling following short term concurrent versus single mode resistance training
Scientific Reports, 2018Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew GarnhamAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT alone. Twenty-three males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor (45S pre-rRNA), and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT. However, during the final training session, RT further increased both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S pre-rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT induces further increases mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in Ribosome Biogenesis markers were more favourable following a period of short-term concurrent training versus RT performed alone.
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enhanced skeletal muscle Ribosome Biogenesis yet attenuated mtorc1 and Ribosome Biogenesis related signalling with concurrent versus single mode resistance training
bioRxiv, 2017Co-Authors: Jackson J Fyfe, David Bishop, Jonathan D Bartlett, Erik D Hanson, Mitchell J Anderson, Andrew Garnham, Nigel K SteptoAbstract:Combining endurance training with resistance training (RT) may attenuate skeletal muscle hypertrophic adaptation versus RT alone; however, the underlying mechanisms are unclear. We investigated changes in markers of Ribosome Biogenesis, a process linked with skeletal muscle hypertrophy, following concurrent training versus RT performed alone. Twenty-three recreationally-active males underwent eight weeks of RT, either performed alone (RT group, n = 8), or combined with either high-intensity interval training (HIT+RT group, n = 8), or moderate-intensity continuous training (MICT+RT group, n = 7). Muscle samples (vastus lateralis) were obtained before training, and immediately before, 1 h and 3 h after the final training session. Training-induced changes in basal expression of the 45S ribosomal RNA (rRNA) precursor, and 5.8S and 28S mature rRNAs, were greater with concurrent training versus RT alone. However, during the final training session, RT induced further increases in both mTORC1 (p70S6K1 and rps6 phosphorylation) and 45S rRNA transcription-related signalling (TIF-1A and UBF phosphorylation) versus concurrent training. These data suggest that when performed in a training-accustomed state, RT preferentially induces mTORC1 and Ribosome Biogenesis-related signalling in human skeletal muscle versus concurrent training; however, changes in skeletal muscle Ribosome Biogenesis markers were more favourable following concurrent training versus RT performed alone.
