title: Peroxiredoxin 1 interacts with and blocks the redox factor APE1 from activating interleukin-8 expression.
abstract: APE1 is an essential DNA repair protein that also possesses the ability to regulate transcription. It has a unique cysteine residue C65, which maintains the reduce state of several transcriptional activators such as NF-κB. How APE1 is being recruited to execute the various biological functions remains unknown. Herein, we show that APE1 interacts with a novel partner PRDX1, a peroxidase that can also prevent oxidative damage to proteins by serving as a chaperone. PRDX1 knockdown did not interfere with APE1 expression level or its DNA repair activities. However, PRDX1 knockdown greatly facilitates APE1 detection within the nucleus by indirect immunofluorescence analysis, even though APE1 level was unchanged. The loss of APE1 interaction with PRDX1 promotes APE1 redox function to activate binding of the transcription factor NF-κB onto the promoter of a target gene, the proinflammatory chemokine IL-8 involved in cancer invasion and metastasis, resulting in its upregulation. Depletion of APE1 blocked the upregulation of IL-8 in the PRDX1 knockdown cells. Our findings suggest that the interaction of PRDX1 with APE1 represents a novel anti-inflammatory function of PRDX1, whereby the association safeguards APE1 from reducing transcription factors and activating superfluous gene expression, which otherwise could trigger cancer invasion and metastasis.
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: Hassan
authors.initials: H
authors.lastname: Nassour
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montréal, Québec, H3T 1E2, Canada.
authors.forename: Amine
authors.initials: A
authors.lastname: Saad
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: Arturo
authors.initials: A
authors.lastname: Papaluca
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Brosseau
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: El Bachir
authors.initials: el B
authors.lastname: Affar
authors.affiliation: Segal Cancer Centre and Lady Davis Institute for Medical Research, Sir Mortimer B. Davis-Jewish General Hospital, 3755 Cote Ste-Catherine Road, Montréal, Québec, H3T 1E2, Canada.
authors.forename: Moulay A
authors.initials: MA
authors.lastname: Alaoui-Jamali
authors.affiliation: Maisonneuve-Rosemont Hospital, Research Center, Université de Montréal, Department of Medicine, 5415 Boul. de l' Assomption, Montréal, Québec, H1T 2M4, Canada.
authors.forename: Dindial
authors.initials: D
authors.lastname: Ramotar
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D018384:Oxidative Stress; D054464:Peroxiredoxins / Q000235:genetics* / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism; D015533:Transcriptional Activation
chemical_list: C508606:CXCL8 protein, human; D016209:Interleukin-8; D016328:NF-kappa B; D006861:Hydrogen Peroxide; C515940:PRDX1 protein, human; D054464:Peroxiredoxins; C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase