Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

Erol, Adnan

doi:10.4161/cc.10.19.17460

Cited by 19 publications

(14 citation statements)

References 109 publications

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“…56,57 Alternatively, torsinA may participate in transcriptional regulation and/or G 1 -S cell-cycle regulation via the TGFb pathway. 58,59 Drosophila larvae that overexpress mutant DE torsinA exhibit overt ultrastructural defects at the neuromuscular junction similar to defects reported for mutants with defective TGFb signaling. 60,61 Overexpression of SMAD2, a downstream effector of the TGFb pathway, corrects morphological and behavioral defects associated with expression of mutant torsinA.…”

Section: Y S T O N I a M O L E C U L A R P A T H W A Y Ssupporting

confidence: 55%

“…These interactions may be important for cell polarity and/or transcription . Alternatively, torsinA may participate in transcriptional regulation and/or G 1 ‐S cell‐cycle regulation via the TGFβ pathway . Drosophila larvae that overexpress mutant ΔE torsinA exhibit overt ultrastructural defects at the neuromuscular junction similar to defects reported for mutants with defective TGFβ signaling .…”

Section: Summary Of Genes and Proteins Involved In Genetic Forms Of Pmentioning

confidence: 99%

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Emerging common molecular pathways for primary dystonia

LeDoux

Dauer

Warner³

2013

Movement Disorders

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Background The dystonias are a group of hyperkinetic movement disorders whose principal cause is neuron dysfunction at one or more interconnected nodes of the motor system. The study of genes and proteins which cause familial dystonia provides critical information about the cellular pathways involved in this dysfunction which disrupts the motor pathways at systems level. In recent years study of the increasing number of DYT genes has implicated a number of cell functions which appear to be involved in the pathogenesis of dystonia. Methods Review of literature published in English language publications available on Pubmed relating to the genetics and cellular pathology of dystonia Results and Conclusions Numerous potential pathogenetic mechanisms have been identified. We describe those which fall into three emerging thematic groups: cell cycle and transcriptional regulation in the nucleus, endoplasmic reticulum and nuclear envelope function, and control of synaptic function.

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Section: Y S T O N I a M O L E C U L A R P A T H W A Y Ssupporting

confidence: 55%

Section: Summary Of Genes and Proteins Involved In Genetic Forms Of Pmentioning

confidence: 99%

Emerging common molecular pathways for primary dystonia

LeDoux

Dauer

Warner³

2013

Movement Disorders

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“…et al, 1998). Given that multiple signaling pathways are triggered by Dox and ionizing radiation, including those which can lead to direct DNA damage, we decided to utilize BrdU as an agent for activating the DDR (Erol, 2011) and inducing senescence for all our subsequent studies. This was essential because both Dox and ionizing radiation are highly toxic (Thorn et al, 2011) and extremely high levels of ROS were detected upon Dox treatment (Fig.…”

Section: Introductionmentioning

confidence: 99%

Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

Nair

Bagheri

Saini

2015

Journal of Cell Science

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Cells exposed to genotoxic stress induce cellular senescence through a DNA damage response (DDR) pathway regulated by ATM kinase and reactive oxygen species (ROS). Here, we show that the regulatory roles for ATM kinase and ROS differ during induction and maintenance of cellular senescence. Cells treated with different genotoxic agents were analyzed using specific pathway markers and inhibitors to determine that ATM kinase activation is directly proportional to the dose of the genotoxic stress and that senescence initiation is not dependent on ROS or the p53 status of cells. Cells in which ROS was quenched still activated ATM and initiated the DDR when insulted, and progressed normally to senescence. By contrast, maintenance of a viable senescent state required the presence of ROS as well as activated ATM. Inhibition or removal of either of the components caused cell death in senescent cells, through a deregulated ATM-ROS axis. Overall, our work demonstrates existence of an intricate temporal hierarchy between genotoxic stress, DDR and ROS in cellular senescence. Our model reports the existence of different stages of cellular senescence with distinct regulatory networks.

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“…Therefore, the expression of this gene is tightly regulated at both the transcriptional and posttranscriptional levels, and in response to various intra-and extra-cellular agents [12,15]. In response to UV light, the CDKN1A mRNA is stabilized by the RNA binding HuR protein [16].…”

Section: Discussionmentioning

confidence: 99%

“…p21 WAF1/Cip1 (hereafter referred to as p21) is a universal cyclin-dependent kinase inhibitor able to interact with most cyclins/CDKs [11]. p21 is encoded by the CDKN1A gene, which is implicated in various cancer-related processes such as cell proliferation, senescence, differentiation, and apoptosis [12][13][14][15]. p21 expression is modulated at different levels, transcriptional, posttranscriptional, and posttranslational, in response to a wide range of intrinsic and extrinsic stimuli [15].…”

Section: Introductionmentioning

confidence: 99%

ATR controls the UV‐related upregulation of the CDKN1A mRNA in a Cdk1/HuR‐dependent manner

Al‐Khalaf

Aboussekhra

2013

Molecular Carcinogenesis

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Ultraviolet (UV) light is a carcinogenic agent that upregulates the expression of several genes involved in various cellular processes, including cell cycle checkpoints and apoptosis. The universal cyclin-dependent kinase inhibitor p21(WAF1/Cip1) plays major roles in these processes, and the level of its corresponding message increases several times in response to UV-induced DNA damage. This upregulation is mainly posttranscriptional owing to HuR-dependent mRNA stabilization. Since the protein kinase Atr plays major roles during the cellular response to UV damage, we sought to investigate its possible implication in the stabilization of the p21(WAF1/Cip1) coding mRNA. We have shown that the UV-dependent accumulation of the CDKN1A mRNA is indeed under the control of the Atr protein kinase. Upon UV damage, Atr allows nuclear-cytoplasmic shuttling of the HuR protein, which binds the CDKN1A mRNA and reduces its turnover. This ATR-dependent effect is mediated through UV-related phosphorylation/inactivation of the Cdk1 protein kinase by Atr, which leads to the dissociation of HuR from Cdk1. Indeed, inhibition or shRNA specific knockdown of CDK1 in ATR-deficient cells enhanced the cytoplasmic level of HuR and restored the CDKN1A mRNA upregulation in response to UV damage. These results show that ATR stabilizes the CDKN1A message in response to UV damage through Cdk1-related cytoplasmic accumulation of HuR.

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Genotoxic stress-mediated cell cycle activities for the decision of cellular fate

Cited by 19 publications

References 109 publications

Emerging common molecular pathways for primary dystonia

Emerging common molecular pathways for primary dystonia

Temporally distinct roles of ATM and ROS in genotoxic-stress-dependent induction and maintenance of cellular senescence

ATR controls the UV‐related upregulation of the CDKN1A mRNA in a Cdk1/HuR‐dependent manner

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