Energy, control and DNA structure in the living cell

Wijker, J.E.; Jensen, Peter Ruhdal; Snoep, Jacky L.; Gomes, Ana Vaz; Guiral, Myriam; Jongsma, A. P. M.; Waal, A. De; Hoving, Sjouke; Dooren, Sonia Van; Weijden, Coen C. van der; Workum, Marielle van; Heeswijk, W.C. van; Molenaar, O.; Wielinga, Peter R.; Richard, Peter; Diderich, Jasper A.; Bakker, Barbara M.; Teusink, Bas; Hemker, Mirte B.; Rohwer, Johann M.; Gugten, A.A. van der; Kholodenko, Boris N.; Westerhoff, Hans V.

doi:10.1016/0301-4622(94)00148-d

Cited by 13 publications

(12 citation statements)

References 83 publications

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“…Recently, similar results have also been found in strains of Escherichia coli , where the ATP/ADP ratio decreases drastically during the S phase of the cell cycle [125]. It is also interesting to consider that in the metabolism of nucleic acids, at the level of the cell nucleus participate dozens of enzymes, the vast majority being ATP dependent [126,127]. This behavior differs completely from that of many glycolytic enzymes, which couple the energy of ATP hydrolysis to favor endergonic reactions.…”

Section: Genetics Epigenetics and Metabolismsupporting

confidence: 57%

“…In addition, the ATP/ADP ratio is essential for all of the processes of chromatin remodeling, and its close dependence has been highlighted by several independent authors [129,130]. In conclusion, an optimal ATP/ADP ratio and an efficient production of ATP are essential for the proper metabolism of nucleic acids [126,127]. …”

Section: Genetics Epigenetics and Metabolismmentioning

confidence: 99%

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Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

Pacini¹,

Borziani²

2014

IJMS

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Over the last 100 years, many studies have been performed to determine the biochemical and histopathological phenomena that mark the origin of neoplasms. At the end of the last century, the leading paradigm, which is currently well rooted, considered the origin of neoplasms to be a set of genetic and/or epigenetic mutations, stochastic and independent in a single cell, or rather, a stochastic monoclonal pattern. However, in the last 20 years, two important areas of research have underlined numerous limitations and incongruities of this pattern, the hypothesis of the so-called cancer stem cell theory and a revaluation of several alterations in metabolic networks that are typical of the neoplastic cell, the so-called Warburg effect. Even if this specific “metabolic sign” has been known for more than 85 years, only in the last few years has it been given more attention; therefore, the so-called Warburg hypothesis has been used in multiple and independent surveys. Based on an accurate analysis of a series of considerations and of biophysical thermodynamic events in the literature, we will demonstrate a homogeneous pattern of the cancer stem cell theory, of the Warburg hypothesis and of the stochastic monoclonal pattern; this pattern could contribute considerably as the first basis of the development of a new uniform theory on the origin of neoplasms. Thus, a new possible epistemological paradigm is represented; this paradigm considers the Warburg effect as a specific “metabolic sign” reflecting the stem origin of the neoplastic cell, where, in this specific metabolic order, an essential reason for the genetic instability that is intrinsic to the neoplastic cell is defined.

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Section: Genetics Epigenetics and Metabolismsupporting

confidence: 57%

Section: Genetics Epigenetics and Metabolismmentioning

confidence: 99%

Cancer Stem Cell Theory and the Warburg Effect, Two Sides of the Same Coin?

Pacini¹,

Borziani²

2014

IJMS

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“…The cellular ATP concentration (and energy charge) has long been known to regulate a multitude of cellular physiological pathways, most notably involving metabolic, mitochondrial, contractile protein, and neuronal functions (17,40,56,57). In stressed cells, the intracellular ATP concentration can drop precipitously from the normal concentration of 5 to 10 mM.…”

Section: Discussionmentioning

confidence: 99%

Human BAG-1 Proteins Bind to the Cellular Stress Response Protein GADD34 and Interfere with GADD34 Functions

Hung

Roberson

Taft

et al. 2003

Molecular and Cellular Biology

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3The cellular stress response protein GADD34 mediates growth arrest and apoptosis in response to DNA damage, negative growth signals, and protein malfolding. GADD34 binds to protein phosphatase PP1 and can attenuate the translational elongation of key transcriptional factors through dephosphorylation of eukaryotic initiation factor 2␣ (eIF2␣). Recently, we reported the involvement of human SNF5/INI1 (hSNF5/INI1) protein in the functions of GADD34 and showed that hSNF5/INI1 binds GADD34 and stimulates the bound PP1 phosphatase activity. To better understand the regulatory and functional mechanisms of GADD34, we undertook a yeast two-hybrid screen with full-length GADD34 as bait in order to identify additional protein partners of GADD34. We report here that human cochaperone protein BAG-1 interacts with GADD34 in vitro and in SW480 cells treated with the proteasome inhibitor z-LLL-B to induce apoptosis. Two other proteins, Hsp70/ Hsc70 and PP1, associate reversibly with the GADD34-BAG-1 complex, and their dissociation is promoted by ATP. BAG-1 negatively modulates GADD34-bound PP1 activity, and the expression of BAG-1 isoforms can also mask GADD34-mediated inhibition of colony formation and suppression of transcription. Our findings suggest that BAG-1 may function to suppress the GADD34-mediated cellular stress response and support a role for BAG-1 in the survival of cells undergoing stress.The eventual fate of cells following exposure to genotoxic stress is determined by signaling from competing pathways favoring either death or survival. The subsequent down-regulation of both p53-dependent and -independent apoptosis pathways may be key to both cell survival and oncogenesis. The growth arrest and DNA damage-inducible protein GADD34 mediates growth arrest and apoptosis in response to stress signals elicited by genotoxic stress, amino acid deprivation, and protein malfolding at the endoplasmic reticulum (21,22,35). The GADD34 transcript is stabilized under conditions of cellular stress, leading to the observed rise in its mRNA level independent of cellular p53 status (24).The GADD34 protein harbors a highly conserved carboxyterminal peptide domain homologous to herpes simplex virus type 1 (HSV-1) ICP34.5, a virulence factor that blocks the premature shutoff of protein synthesis in HSV-1-infected neuroblastoma cells and allows HSV-1-infected cells to circumvent apoptosis (6,10,11,19). Both ICP34.5 and mammalian GADD34 engage protein phosphatase-1 (PP1) and target dephosphorylation of the eukaryotic translation elongation factor eIF2␣ (13,20). In HSV-1-infected cells, this molecular event enables protein synthesis (19). In mammalian cells, the dephosphorylation attenuates eIF2␣-mediated induction of stress-responsive genes and has been proposed in feedback regulation of cellular stress response initiated by protein malfolding at the endoplasmic reticulum (35).The mechanism and regulation of GADD34-mediated growth suppression and apoptosis remain poorly understood.Recently we reported the association of the human SNF5...

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“…(1997) is of a different type. It extends our understanding of the control of metabolic #uxes to include the levels of signal transduction and gene expression (Wijker et al, 1995). This of course is essential for functional genome analysis (Teusink et al, 1998).…”

Section: Discussionmentioning

confidence: 99%