A new APE1/Ref-1-dependent pathway leading to reduction of NF- B and AP-1, and activation of their DNA-binding activity

Ando, Kozue; Hirao, Satoshi; Kabe, Yoshio; Ogura, Yuji; Satō, Iwao; Yamaguchi, Yuki; Wada, Tadashi; Handa, Hiroshi

doi:10.1093/nar/gkn416

Cited by 133 publications

(122 citation statements)

References 55 publications

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“…This protein is the rate-limiting enzyme in the BER pathway (Hoeijmakers, 2001). In addition to its role in DNA repair, APE1/Ref-1 also functions as a redox activator of numerous cellular transcription factors that are thought to be important in carcinogenesis, including AP-1, NF-kB, Myb, HIF-1a, HLF, PAX, and p53 (Ando et al, 2008). Polymorphisms in a promoter region can influence interactions between transcriptional factors and their ability to recognize DNA sequences in a promoter region, and thus affect gene expression.…”

Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population

Luo¹,

Li²,

Qu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Altered DNA repair capacity can result in increased susceptibility to cancer. The base excision repair (BER) pathway effectively removes DNA damage caused by ionizing radiation and reactive oxidative species (ROS). In the current study, we analyzed the possible relation of polymorphisms in BER genes, including 8-oxoguanine DNA glycosylase (OGG1), apurinic/apyrimidinic endonuclease 1 (APE1), and X-ray repair cross-complementing group 1 protein (XRCC1), with breast cancer risk in Chinese Han women. This case-control study examined 194 patients with breast cancer and 245 cancer-free hospitalized control subjects. Single nucleotide polymorphisms (SNPs) of OGG1 (Ser326Cys), XRCC1 (Arg399Gln), and APE1 (Asp148Glu and -141T/G) were genotyped and analyzed for their association with breast cancer risk using multivariate logistic regression models. We found that XRCC1 Arg399Gln was significantly associated with an increased risk of breast cancer. Similarly, the XRCC1 Gln allele was significantly associated with an elevated risk in postmenopausal women and women with a high BMI (≥ 24 kg/m 2 ). The OGG1 Cys allele provided a significant protective effect against developing cancer in women with a low BMI (< 24 kg/m 2 ). When analyzing the combined effects of these alleles on the risk of breast cancer, we found that individuals with ≥ 2 adverse genotypes (XRCC1 399Gln, APE1 148Asp, and OGG1 326Ser) were at a 2.18-fold increased risk of breast cancer (P = 0.027). In conclusion, our data indicate that Chinese women with the 399Gln allele of XRCC1 have an increased risk of breast cancer, and the combined effects of polymorphisms of BER genes may contribute to tumorigenesis.

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Section: Discussionmentioning

confidence: 99%

Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population

Luo¹,

Li²,

Qu³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Ape1 was originally identified as a DNA repair enzyme with apurinic and apyrimidinic endonuclease activity in the base excision repair pathway (Bhakat et al, 2009;. The redox state of cysteine residues in the DNA-binding domain of several transcription factors, such as Erg-1 (Fantini et al, 2008), HIF-1a (Huang et al, 1996), p53 (Gaiddon et al, 1999) and nuclear factor (NF)-kB p50 subunit (Nishi et al, 2002;Ando et al, 2008), has been shown to affect DNA binding. NF-kB is a transcription factor important for the expression of numerous genes contributing to inflammation, and innate and adaptive immune responses (Aggarwal, 2004;Karin, 2006).…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-κB activation

Cheng

Chang

et al. 2010

Oncogene

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Apurinic endonuclease 1 (Ape1) is not only involved in base excision repair, but also activates some transcriptional factors through its redox activity. However, which subcellular localization of Ape1 is involved in the activation of transcriptional factor remains unclear. We first observed that Cox-2 expression was associated with cytoplasmic Ape1 expression in lung tumors and cancer cell lines. We thus hypothesize that nuclear factor (NF)-jB is activated by cytoplasmic Ape1 to cause Cox-2 expression. Herein, we generated cytoplasmic and nuclear Ape1 in Ape1-knockdown lung cancer cells by exogenous expression of Ape1 containing various deletions and/or mutations of the nuclear localization sequence. It was observed that cytoplasmic Ape1, but not nuclear Ape1, induced Cox-2 expression through NF-jB activation. NF-jB activation by cytoplasmic Ape1 was diminished by the Ape1 redox activity inhibitor resveratrol. Cells expressing cytoplasmic Ape1 exhibited tumor progression and metastasis in vitro and in vivo as xenografts, but cells expressing nuclear Ape1 did not. Patients with tumors containing elevated cytoplasmic Ape1 had a poor prognosis and a 3.722-fold risk of tumor recurrence and/or metastasis. Cytoplasmic Ape1 could therefore enhance lung tumor malignancy through NF-jB activation, suggesting that combination of cisplatin and specific redox inhibitor could improve chemotherapeutic response in patients with tumors containing elevated cytoplasmic Ape1.

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“…Cys62 within the N-terminal region of p50 has been identified as the pivotal residue (483), which was a surprise, since this cysteine is most easily oxidized in the cytoplasm. However, when NF-jB has entered the nucleus, Cys62 is rapidly reduced by either Trx/TrxR (169,184,315) or apyrimidinic endonuclease 1/redox factor 1 (APE1/Ref-1) (7,346). Similarly, NF-jB, which is translocated to mitochondria upon stimulation by apoptotic signals, including TNFa (529), is kept active via reduction of p65 by Trx2 (386).…”

Section: Brigelius-flohé and Flohémentioning

confidence: 99%

Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors

Brigelius‐Flohé

Flohé

2011

Antioxidants & Redox Signaling

522

442

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Convincing concepts of redox control of gene transcription have been worked out for prokaryotes and lower eukaryotes, whereas the knowledge on complex mammalian systems still resembles a patchwork of poorly connected findings. The article, therefore, reviews principles of redox regulation with special emphasis on chemical feasibility, kinetic requirements, specificity, and physiological context, taking well investigated mammalian transcription factor systems, nuclear transcription factor of bone marrow-derived lymphocytes (NFjB), and kelch-like ECH-associated protein-1 (Keap1)/Nrf2, as paradigms. Major conclusions are that (i) direct signaling by free radicals is restricted to O 2 -and NO and can be excluded for fast reacting radicals such as OH, OR, or Cl ; (ii) oxidant signals are H 2 O 2 , enzymatically generated lipid hydroperoxides, and peroxynitrite; (iii) free radical damage is sensed via generation of Michael acceptors; (iv) protein thiol oxidation/alkylation is the prominent mechanism to modulate function; (v) redox sensors must be thiol peroxidases by themselves or proteins with similarly reactive cysteine or selenocysteine (Sec) residues to kinetically compete with glutathione peroxidase (GPx)-and peroxiredoxin (Prx)-type peroxidases or glutathione-S-transferases, respectively, a postulate that still has to be verified for putative mammalian sensors. S-transferases and Prxs are considered for system complementation. The impact of NF-jB and Nrf2 on hormesis, management of inflammatory diseases, and cancer prevention is critically discussed. Antioxid. Redox Signal. 15, 2335-2381.

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A new APE1/Ref-1-dependent pathway leading to reduction of NF- B and AP-1, and activation of their DNA-binding activity

Cited by 133 publications

References 55 publications

Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population

Single Nucleotide Polymorphisms of DNA Base-excision Repair Genes (APE1, OGG1 and XRCC1) Associated with Breast Cancer Risk in a Chinese Population

Subcellular localization of apurinic endonuclease 1 promotes lung tumor aggressiveness via NF-κB activation

Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors

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