Checkpoint control and cancer

Medema, René H.; Macůrek, Libor

doi:10.1038/onc.2011.451

Cited by 147 publications

(168 citation statements)

References 152 publications

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“…The cell cycle with its various check point proteins sees to it that the abnormal cells do not divide in the body. The cell cycle is either arrested to correct the DNA repairs in the abnormal cells or the cells are forced to undergo apoptosis (Medema & Macurek, 2011). The cell cycle check points are lost in cancer and hence the cells proliferate at a very high rate (Hartwell and Kastan, 1994).…”

Section: Mif and Cell Cyclementioning

confidence: 99%

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

Babu¹,

Chetal²,

Kumar³

2012

Asian Pacific Journal of Cancer Prevention

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Macrophage migration inhibitory factor (MIF) is a pluripotent cytokine which plays roles in inflammation, immune responses and cancer development. It assists macrophages in carrying out functions like phagocytosis, adherence and motility. Of late, MIF is implicated in almost all stages of neoplasia and expression is a feature of most types of cancer. The presence of MIF in almost all tumors and all stages of cancer makes it an interesting candidate for cancer therapy. This review explores the roles of MIF in neoplasia.

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Section: Mif and Cell Cyclementioning

confidence: 99%

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

Babu¹,

Chetal²,

Kumar³

2012

Asian Pacific Journal of Cancer Prevention

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“…3F and G). DNA damage can trigger a p53-dependent or independent cell cycle arrest (42). In MCF7, ARIH1 knockdown did not alter basal cell cycle distribution or CP-induced increase in S/G 2 ( Fig.…”

Section: A Ubiquitination Rnai Screen Identifies Cp Response Modulatorsmentioning

confidence: 99%

The E3 Ubiquitin Ligase ARIH1 Protects against Genotoxic Stress by Initiating a 4EHP-Mediated mRNA Translation Arrest

Stechow

Typas

Carreras-Puigvert

et al. 2015

Molecular and Cellular Biology

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bDNA damage response signaling is crucial for genome maintenance in all organisms and is corrupted in cancer. In an RNA interference (RNAi) screen for (de)ubiquitinases and sumoylases modulating the apoptotic response of embryonic stem (ES) cells to DNA damage, we identified the E3 ubiquitin ligase/ISGylase, ariadne homologue 1 (ARIH1). Silencing ARIH1 sensitized ES and cancer cells to genotoxic compounds and ionizing radiation, irrespective of their p53 or caspase-3 status. Expression of wild-type but not ubiquitinase-defective ARIH1 constructs prevented sensitization caused by ARIH1 knockdown. ARIH1 protein abundance increased after DNA damage through attenuation of proteasomal degradation that required ATM signaling. Accumulated ARIH1 associated with 4EHP, and in turn, this competitive inhibitor of the eukaryotic translation initiation factor 4E (eIF4E) underwent increased nondegradative ubiquitination upon DNA damage. Genotoxic stress led to an enrichment of ARIH1 in perinuclear, ribosome-containing regions and triggered 4EHP association with the mRNA 5= cap as well as mRNA translation arrest in an ARIH1-dependent manner. Finally, restoration of DNA damage-induced translation arrest in ARIH1-depleted cells by means of an eIF2 inhibitor was sufficient to reinstate resistance to genotoxic stress. These findings identify ARIH1 as a potent mediator of DNA damage-induced translation arrest that protects stem and cancer cells against genotoxic stress. DNA damage leads to acute toxicity and the accumulation of mutations and chromosomal instability, potentially resulting in malignant transformation (1, 2). To counteract these deleterious effects of DNA damage, the cell is equipped with a highly complex signaling response termed the DNA damage response (DDR). The DDR activates effector components involved in protective pathways, including DNA damage repair, cell cycle arrest, transcription regulation, chromatin remodeling, and cell death (1). The complex of DDR signaling pathways is crucial for the protection of the genome in all organisms. Moreover, understanding DDR signaling in the context of chemical or ionizing radiation-induced DNA damage is important to design improved strategies to combat therapy resistance. In tandem with phosphorylation-mediated signaling, which is largely executed by the phosphoinositol 3-kinase (PI3K)-like kinases ATM, ATR, and DNA-dependent protein kinase (DNA-PK), the checkpoint kinases Chk1 and Chk2, and members of the mitogen-activated protein kinase (MAPK) family (3, 4), protein modifications by ubiquitin and ubiquitin-like moieties are crucial at all levels of the DDR (5).The ubiquitination machinery can form various, differentially interpreted tags, including both degradative (K48-and K11-linked chains) and nondegradative (monoubiquitination and K63-linked chains) signals (6). Furthermore, a growing family of ubiquitin-like modifications, such as SUMO, Nedd8, and ISG15, has been identified, mostly providing nondegradative signals. Multiple enzymes are shared between the ubiquitinat...

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“…Other microRNAs were also related to regulatory mechanism DNA damage repair or radiosensitivity. MicroRNA-101 was associated with DNA-dependent protein kinase catalytic subunit (DNA-PKcs) and ATM to sensitize neoplasms to radioation; 59,60 microRNA-210 and miR-373 are overexpressed in hypoxic cells and regulate the expression of various aspects in DNA damage repair pathways; 61,62 microRNA-125b, microRNA-504, and microRNA-33 were correlated to p53 (one major factor in DNA-damage checkpoint activation); 63,64 microRNA-421 downregulation of ATM leading to clinical manifest tumor radiosensitivity in head and neck squamous cell carcinoma; 65 microRNA-7 increases radiosensitivity of human tumor cells with activated epidermal growth factor receptor (EGFR) associated signaling; 66 microRNA-221 and microRNA-222 control radiation sensitivity by controlling the PTEN/Akt pathway; 67 microRNAs (-155, -20a, -25, and -15a) are involved in the regulation of IR-induced premature senescence; 68 lin28-let7 modulates radiosensitivity of human cancer cells with activation of K-Ras. 69 In conclusion, it is not very clear if the global mechanism of microRNA disturbs sensitivity to radiation, but it is evidence that cellular radiosensitivity could indeed be influenced by microRNAs.…”

Section: Microrna Changes After Irmentioning

confidence: 99%

MicroRNAs, cancer and ionizing radiation: Where are we?

Marta

Garicochea

Carvalho

et al. 2015

Rev. Assoc. Med. Bras.

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Conflict of interest: noneThe aim of this study is to describe the biogenesis of microRNA, its relations with carcinogenesis, and the correlation between microRNA and ionizing radiation (IR), focusing on radioresponsiveness. It is known that microRNA biogenesis is well established and involves different enzymatic cleavages, resulting in the production of mature microRNA. MicroRNAs are involved in carcinogenesis. Their interaction is related to the genetic and epigenetic changes associated with activation of proto-oncogenes or inactivation of tumor suppressor genes. Several studies have shown that the levels of expression of some microRNAs vary significantly after irradiation. There are evidences that microRNAs can influence cellular response after IR. In addition, microRNAs are related to modulation of the expression of several post-transcriptional targets in DNA damage response pathways, and to the DNA damage repair regulation mechanism. Future studies can clarify a possible clinical use of microRNAs as a new class of radiosensitive agents.

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Checkpoint control and cancer

Cited by 147 publications

References 152 publications

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

Macrophage Migration Inhibitory Factor: a Potential Marker for Cancer Diagnosis and Therapy

The E3 Ubiquitin Ligase ARIH1 Protects against Genotoxic Stress by Initiating a 4EHP-Mediated mRNA Translation Arrest

MicroRNAs, cancer and ionizing radiation: Where are we?

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