ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence

Weyemi, Urbain; Lagente-Chevallier, Odile; Boufraqech, Myriem; Prenois, F; Courtin, Françoise; Caillou, Bernard; Talbot, Monique; Dardalhon, M.; Ghuzlan, A. Al; Bidart, Jean Michel; Schlumberger, M.; Dupuy, Corinne

doi:10.1038/onc.2011.327

Cited by 245 publications

(212 citation statements)

References 45 publications

Supporting

Mentioning

196

Contrasting

Unclassified

Order By: Relevance

“…This result is consistent with effects of p22 phox on DNA damage seen in H-RAS-transfected cells, where the knockdown of p22 phox resulted in a decrease in DNA DSBs (36). Together these data suggest that NOX-produced H 2 O 2 is directly responsible for causing DNA damage in the nucleus.…”

Section: Discussionsupporting

confidence: 80%

“…Similar to what we observe in FLT3-ITD expressing cells, H-RAS-induced increased NOX4 expression is accompanied by an increase in the nuclear H 2 O 2 and DNA DSBs (36). We suggest that a similar mechanism operates in FLT3-ITD-expressing cells where increased levels of NOX proteins generate an ROS burst that causes DNA damage.…”

Section: Discussionsupporting

confidence: 68%

“…We have also shown that p22 phox localizes to the nuclear membrane (Fig. 6C), which is consistent with p22 phox co-localization to A/C lamin in the H-RAS-expressing cells (36). Therefore, we postulate that NOX4/p22 phox -derived H 2 O 2 diffuses from the nuclear membrane to the nucleus in these cells.…”

Section: Discussionsupporting

confidence: 67%

“…Leukemic oncogenes have been shown to regulate either the expression of NOX components or the availability of their substrate. For example, overexpression of H-RAS has been shown to increase NOX4 expression (36). Interestingly, cells expressing FLT3-ITD have been reported to possess an increased concentration of NADPH (27).…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

NADPH Oxidase-generated Hydrogen Peroxide Induces DNA Damage in Mutant FLT3-expressing Leukemia Cells

Stanicka

Russell

Woolley

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: NADPH oxidase is a hydrogen peroxide-generating enzyme, involved in redox signaling in cancer. Results: NADPH oxidase-generated hydrogen peroxide increases DNA damage and genomic instability. Conclusion: NADPH oxidase-derived hydrogen peroxide mediates DNA damage in acute myeloid leukemia (AML). Significance: The mechanism of DNA damage generation is important for studying aggressive AML phenotypes.

show abstract

Section: Discussionsupporting

confidence: 80%

Section: Discussionsupporting

confidence: 68%

Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

NADPH Oxidase-generated Hydrogen Peroxide Induces DNA Damage in Mutant FLT3-expressing Leukemia Cells

Stanicka

Russell

Woolley

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Effects of this type are not confined to fibroblasts. In human thyrocytes, NAPD H oxidase Nox4 has been shown to maintain a DDR during OIS through the generation of ROS (Weyemi et al 2012). It has also been shown in U2OS cells and BJ fibroblasts that induction of ROS and DDR via Nox4 drives induction of senescence in growth-competent nearby cells (the so-called Bbystander effect^), a process regulated by secretory factors such as IL-1 (Weyemi et al 2012;Hubackova et al 2012).…”

Section: Cell Cycle Arrestmentioning

confidence: 99%

Cellular senescence: from growth arrest to immunogenic conversion

Burton

Faragher

2015

AGE

View full text Add to dashboard Cite

Cellular senescence was first reported in human fibroblasts as a state of stable in vitro growth arrest following extended culture. Since that initial observation, a variety of other phenotypic characteristics have been shown to co-associate with irreversible cell cycle exit in senescent fibroblasts. These include (1) a proinflammatory secretory response, (2) the up-regulation of immune ligands, (3) altered responses to apoptotic stimuli and (4) promiscuous gene expression (stochastic activation of genes possibly as a result of chromatin remodeling). Many features associated with senescent fibroblasts appear to promote conversion to an immunogenic phenotype that facilitates self-elimination by the immune system. Pro-inflammatory cytokines can attract and activate immune cells, the presentation of membrane bound immune ligands allows for specific recognition and promiscuous gene expression may function to generate an array of tissue restricted proteins that could subsequently be processed into peptides for presentation via MHC molecules. However, the phenotypes of senescent cells from different tissues and species are often assumed to be broadly similar to those seen in senescent human fibroblasts, but the data show a more complex picture in which the growth arrest mechanism, tissue of origin and species can all radically modulate this basic pattern. Furthermore, wellestablished triggers of cell senescence are often associated with a DNA damage response (DDR), but this may not be a universal feature of senescent cells. As such, we discuss the role of DNA damage in regulating an immunogenic response in senescent cells, in addition to discussing less established Batypical^senescent states that may occur independent of DNA damage.

show abstract

In Cellular Senescence, the Third Circle of the Cell Life's Network, p53 Acts Vital Role

İzmirli

2017

Encyclopedia of Life Sciences

View full text Add to dashboard Cite

The cells rotationally live as Gap 1 (G1), DNA (deoxyribonucleic acid) synthesis (S), Gap 2(G2) and mitosis (M). In response to DNA damage, telomere‐shortening proliferating cells enter the quiescence phase (G0) in which DNA is repaired. If DNA is repaired, the cell can reenter the cell cycle. However, if DNA has double‐strand DNA damage, cellular senescence appears. Thus, cellular senescence is a cell cycle process in which abnormal, DNA‐damaged or ageing cells are gripped irreversibly and permanently during cell cycle as a common stress reaction. Cellular senescence is of five groups according to initiating factor of senescence: replicative senescence, metabolic stress‐induced senescence, DNA damage‐induced senescence, Fas ligand‐induced senescence and oncogene‐induced senescence. Moreover, there are some biomarkers such as p53, p21, mTOR (mechanistic target of rapamycin), ATM/ATR and pRB for senescence. However, the molecular mechanism underlying senescence has been revealed; however, answers have not arisen regarding the precise nature and physiological significance of the senescence for years. Thus, these processes are highlighted in which recent studies of cell cycle events might need to be reviewed with recent molecular studies of senescence by emphasising the key molecular players, p53 and p53‐dependent players. Key Concepts What is cell cycle and life? Why do cells choose senescence or quiescence or apoptosis? How do cells choose senescence? When do cells choose senescence? Which cells choose senescence? Which important hallmarks do change during cellular apoptosis? Which physiological things do occur during cellular apoptosis? Does the alteration of senescence cause pathological situations?

show abstract

ROS-generating NADPH oxidase NOX4 is a critical mediator in oncogenic H-Ras-induced DNA damage and subsequent senescence

Cited by 245 publications

References 45 publications

NADPH Oxidase-generated Hydrogen Peroxide Induces DNA Damage in Mutant FLT3-expressing Leukemia Cells

NADPH Oxidase-generated Hydrogen Peroxide Induces DNA Damage in Mutant FLT3-expressing Leukemia Cells

Cellular senescence: from growth arrest to immunogenic conversion

In Cellular Senescence, the Third Circle of the Cell Life's Network, p53 Acts Vital Role

Contact Info

Product

Resources

About