Human ARHI / DIRAS3 Protein (Fc Tag)

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Human ARHI / DIRAS3 Protein (Fc Tag) Catalog Number: 14239-H04H General Information SDS-PAGE: Gene Name Synonym: ARHI; DIRAS3; NOEY2; RHOI Protein Construction: A DNA sequence encoding the human DIRAS3 (O95661) (Met1-Lys225) was expressed with the Fc region of mouse IgG1 at the N-terminus. Source: Human Expression Host: HEK293 Cells QC Testing Purity: > 85 % as determined by SDS-PAGE Endotoxin: Protein Description < 1.0 EU per μg of the protein as determined by the LAL method ARHI, also known as DIRAS3, belongs to the small GTPase superfamily, Stability: Di-Ras family. ARHI gene is a novel tumor suppressor gene located on chromosome 1p31. Downregulation of ARHI expression has been detected Samples are stable for up to twelve months from date of receipt at -70 ℃ in many types of cancer. ARHI is expressed in normal ovarian and breast epithelial cells but not in ovarian and breast cancers. As a suppressor, Predicted N terminal: Asp ARHI is not only an important factor in the pathogenesis of gastric cancer, Molecular Mass: but also a potential factor for tumor aggravation. ARHI expression in gastric cancer can be employed to indicate favorable prognosis for the disease. The recombinant human DIRAS3/mFc comprises 461 amino acids and has a predicted molecular mass of 52.1 kDa. The apparent molecular References mass of the monomer is approximately 62 kDa in SDS-PAGE under 1.Pei XH. et al., 2011, Cell Biol Int. 35 (10): 1019-24. 2.Lin D. et al., 2011, reducing conditions due to glycosylation. J Int Med Res. 39 (5): 1870-5. 3.Wang W. et al., 2012, Oncol Rep. 27 (6): Formulation: 1953-9. Lyophilized from sterile PBS, pH 7.4. Normally 5 % - 8 % trehalose, mannitol and 0.01% Tween80 are added as protectants before lyophilization. Specific concentrations are included in the hardcopy of COA. Please contact us for any concerns or special requirements. Usage Guide Storage: Store it under sterile conditions at -20℃ to -80℃ upon receiving. Recommend to aliquot the protein into smaller quantities for optimal storage. Avoid repeated freeze-thaw cycles. Reconstitution: Detailed reconstitution instructions are sent along with the products. Manufactured By Sino Biological Inc., FOR RESEARCH USE ONLY. NOT FOR USE IN HUMANS. For US Customer： Fax: 267-657-0217 Tel：215-583-7898 Global Customer： Fax :+86-10-5862-8288 Tel:+86-400-890-9989 http://www.sinobiological.com.

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DIRAS3 Antibody Catalog # ASC11908
10320 Camino Santa Fe, Suite G San Diego, CA 92121 Tel: 858.875.1900 Fax: 858.622.0609 DIRAS3 Antibody Catalog # ASC11908 Specification DIRAS3 Antibody - Product Information Application WB Primary Accession O95661 Other Accession NP_004666, 4757772 Reactivity Human Host Rabbit Clonality Polyclonal Isotype IgG Calculated MW Predicted: 25 kDa Observed: 24 kDa KDa Application Notes DIRAS3 antibody can be used for detection of DIRAS3 by Western blot at 1 Western blot analysis of DIRAS3 in human - 2 µg/ml. testis tissue lysate with DIRAS3 antibody at 1 µg/ml. DIRAS3 Antibody - Additional Information DIRAS3 Antibody - Background Gene ID 9077 Target/Specificity DIRAS3 is a member of the ras superfamily, DIRAS3; DIRAS3 antibody is human specific. and is expressed in normal ovarian and breast epithelial cells, but not in ovarian and breast Reconstitution & Storage cancers. It is an imprinted gene, with DIRAS3 antibody can be stored at 4℃ for mono-allelic expression of the paternal allele, three months and -20℃, stable for up to which is associated with growth suppression one year. and down-regulation of cyclin D1 promoter Precautions activity and induction of p21 (WAF/CIP1). Thus, DIRAS3 Antibody is for research use only this gene appears to be a putative tumor and not for use in diagnostic or therapeutic suppressor gene whose function is abrogated procedures. in ovarian and breast cancers (1). DIRAS3 has been shown to induce autophagy in human ovarian cancer cells by blocking PI3K signaling, inhibiting the mammalian target of rapamycin DIRAS3 Antibody - Protein Information (TOR), upregulating ATG4, and colocalizing with LC3 in autophagosomes (2). DIRAS also Name DIRAS3 interacts with C-RAF and downregulates mitogen-activated protein kinase kinases Synonyms ARHI, NOEY2, RHOI (MEK) to restrict cell migration (3).
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DIRAS3 Antibody Cat
DIRAS3 Antibody Cat. No.: 8139 DIRAS3 Antibody Specifications HOST SPECIES: Rabbit SPECIES REACTIVITY: Human DIRAS3 antibody was raised against an 18 amino acid peptide near the carboxy terminus of human DIRAS3. IMMUNOGEN: The immunogen is located within the last 50 amino acids of DIRAS3. TESTED APPLICATIONS: ELISA, WB DIRAS3 antibody can be used for detection of DIRAS3 by Western blot at 1 - 2 μg/ml. APPLICATIONS: Antibody validated: Western Blot in human samples. All other applications and species not yet tested. SPECIFICITY: DIRAS3 antibody is human specific. POSITIVE CONTROL: 1) Cat. No. 1313 - Human Testis Tissue Lysate Predicted: 25 kDa PREDICTED MOLECULAR WEIGHT: Observed: 24 kDa Properties September 26, 2021 1 https://www.prosci-inc.com/diras3-antibody-8139.html PURIFICATION: DIRAS3 antibody is affinity chromatography purified via peptide column. CLONALITY: Polyclonal ISOTYPE: IgG CONJUGATE: Unconjugated PHYSICAL STATE: Liquid BUFFER: DIRAS3 antibody is supplied in PBS containing 0.02% sodium azide. CONCENTRATION: 1 mg/mL DIRAS3 antibody can be stored at 4˚C for three months and -20˚C, stable for up to one STORAGE CONDITIONS: year. Additional Info OFFICIAL SYMBOL: DIRAS3 ALTERNATE NAMES: DIRAS family GTP-binding RAS-like 3, ARHI, NOEY2 ACCESSION NO.: NP_004666 PROTEIN GI NO.: 4757772 GENE ID: 9077 USER NOTE: Optimal dilutions for each application to be determined by the researcher. Background and References DIRAS3 is a member of the ras superfamily, and is expressed in normal ovarian and breast epithelial cells, but not in ovarian and breast cancers. It is an imprinted gene, with mono-allelic expression of the paternal allele, which is associated with growth suppression and down-regulation of cyclin D1 promoter activity and induction of p21 (WAF/CIP1).
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GNG12-AS1 Uncouples Its Transcriptional and Product-Related Functions
ARTICLE Received 4 Sep 2015 | Accepted 8 Dec 2015 | Published 2 Feb 2016 DOI: 10.1038/ncomms10406 OPEN Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions Lovorka Stojic1, Malwina Niemczyk1, Arturo Orjalo2,w, Yoko Ito1, Anna Elisabeth Maria Ruijter1, Santiago Uribe-Lewis1, Nimesh Joseph1, Stephen Weston3, Suraj Menon1, Duncan T. Odom1, John Rinn4, Fanni Gergely1 & Adele Murrell1,3 Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1,a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3. Here we show that while most siRNAs silence GNG12-AS1 post-transcriptionally, siRNA complementary to exon 1 of GNG12-AS1 suppresses its transcription by recruiting Argonaute 2 and inhibiting RNA polymerase II binding. Transcriptional, but not post-transcriptional, silencing of GNG12-AS1 causes concomitant upregulation of DIRAS3, indicating a function in transcriptional interference. This change in DIRAS3 expression is sufﬁcient to impair cell cycle progression. In addition, the reduction in GNG12-AS1 transcripts alters MET signalling and cell migration, but these are independent of DIRAS3. Thus, differential siRNA targeting of a lncRNA allows dissection of the functions related to the process and products of its transcription. 1 Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Robinson Way, Cambridge CB2 0RE, UK. 2 Biosearch Technologies Inc., 2199S. McDowell Boulevard, Petaluma, California 94954, USA. 3 Centre for Regenerative Medicine, Department of Biology and Biochemistry, University of Bath, Claverton Down, Bath BA2 7AY, UK.
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ARHI (DIRAS3), an Imprinted Tumour Suppressor Gene, Binds to Importins and Blocks Nuclear Import of Cargo Proteins
Biosci. Rep. (2010) / 30 / 159–168 (Printed in Great Britain) / doi 10.1042/BSR20090008 ARHI (DIRAS3), an imprinted tumour suppressor gene, binds to importins and blocks nuclear import of cargo proteins Shaoyi HUANG*, In Soon CHANG†, Wenbo LIN§, Wenduo YE§, Robert Z. LUO*, Zhen LU*, Yiling LU‡, Ke ZHANG†, Warren S.-L. LIAO*, Tao TAO§, Robert C. BAST, Jr*, Xiaomin CHEN† and Yinhua YU*1 *Department of Experimental Therapeutics, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, U.S.A., †Department of Biochemistry and Molecular Biology, The University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, U.S.A., ‡Department of Systems Biology, The University of Texas, M.D. Anderson Cancer Center, Houston, Texas 77030, U.S.A., §School of Life Sciences, Xiamen University, Xiamen, Fujian 361005, People’s Republic of China, and Obstetrics and Gynecology Hospital of Fudan University, Shanghai 200011, People’s Republic of China ' $ Synopsis ARHI (aplasia Ras homologue member I; also known as DIRAS3) is an imprinted tumour suppressor gene, the expression of which is lost in the majority of breast and ovarian cancers. Unlike its homologues Ras and Rap, ARHI functions as a tumour suppressor. Our previous study showed that ARHI can interact with the transcriptional activator STAT3 (signal transducer and activator of transcription 3) and inhibit its nuclear translocation in human breast- and ovarian-cancer cells. To identify proteins that interact with ARHI in nuclear translocation, in the present study, we performed proteomic analysis and identified several importins that can associate with ARHI. To further explore this novel finding, we purified 10 GST (glutathione transferase)–importin fusion proteins (importins 7, 8, 13, β1, α1, α3, α5, α6, α7 and mutant α1).
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Transcriptional Silencing of Long Noncoding RNA GNG12-AS1 Uncouples Its Transcriptional and Product-Related Functions.” Nature Communications 7 (1): 10406
Transcriptional silencing of long noncoding RNA GNG12- AS1 uncouples its transcriptional and product-related functions The Harvard community has made this article openly available. Please share how this access benefits you. Your story matters Citation Stojic, L., M. Niemczyk, A. Orjalo, Y. Ito, A. E. M. Ruijter, S. Uribe- Lewis, N. Joseph, et al. 2016. “Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions.” Nature Communications 7 (1): 10406. doi:10.1038/ncomms10406. http://dx.doi.org/10.1038/ncomms10406. Published Version doi:10.1038/ncomms10406 Citable link http://nrs.harvard.edu/urn-3:HUL.InstRepos:26318707 Terms of Use This article was downloaded from Harvard University’s DASH repository, and is made available under the terms and conditions applicable to Other Posted Material, as set forth at http:// nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of- use#LAA ARTICLE Received 4 Sep 2015 | Accepted 8 Dec 2015 | Published 2 Feb 2016 DOI: 10.1038/ncomms10406 OPEN Transcriptional silencing of long noncoding RNA GNG12-AS1 uncouples its transcriptional and product-related functions Lovorka Stojic1, Malwina Niemczyk1, Arturo Orjalo2,w, Yoko Ito1, Anna Elisabeth Maria Ruijter1, Santiago Uribe-Lewis1, Nimesh Joseph1, Stephen Weston3, Suraj Menon1, Duncan T. Odom1, John Rinn4, Fanni Gergely1 & Adele Murrell1,3 Long noncoding RNAs (lncRNAs) regulate gene expression via their RNA product or through transcriptional interference, yet a strategy to differentiate these two processes is lacking. To address this, we used multiple small interfering RNAs (siRNAs) to silence GNG12-AS1,a nuclear lncRNA transcribed in an antisense orientation to the tumour-suppressor DIRAS3.
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NNAT and DIRAS3 Genes Are Paternally Expressed in Pigs Huan-Chen Cheng, Feng-Wei Zhang, Chang-Yan Deng, Cao-De Jiang, Yuan-Zhu Xiong, Feng-E Li, Ming-Gang Lei
NNAT and DIRAS3 genes are paternally expressed in pigs Huan-Chen Cheng, Feng-Wei Zhang, Chang-Yan Deng, Cao-De Jiang, Yuan-Zhu Xiong, Feng-E Li, Ming-Gang Lei To cite this version: Huan-Chen Cheng, Feng-Wei Zhang, Chang-Yan Deng, Cao-De Jiang, Yuan-Zhu Xiong, et al.. NNAT and DIRAS3 genes are paternally expressed in pigs. Genetics Selection Evolution, BioMed Central, 2007, 39 (5), pp.599-607. hal-00894607 HAL Id: hal-00894607 https://hal.archives-ouvertes.fr/hal-00894607 Submitted on 1 Jan 2007 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Genet. Sel. Evol. 39 (2007) 599–607 Available online at: c INRA, EDP Sciences, 2007 www.gse-journal.org DOI: 10.1051/gse:2007024 Original article NNAT and DIRAS3 genes are paternally expressed in pigs Huan-Chen Ca, Feng-Wei Zhanga, Chang-Yan Da∗, Cao-De Jb, Yuan-Zhu Xa, Feng-E La, Ming-Gang La a Key Laboratory of Agricultural Animal Genetics, Breeding and Reproduction of Ministry of Education and Key Laboratory of Swine Genetics and Breeding of Ministry of Agriculture, Huazhong Agriculture University, Wuhan, P. R.
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Gene Section Review
Atlas of Genetics and Cytogenetics in Oncology and Haematology OPEN ACCESS JOURNAL AT INIST-CNRS Gene Section Review DIRAS3 (DIRAS family, GTP -binding RAS -like 3) Yinhua Yu, Zhen Lu, Robert Z Luo, Robert C Bast Jr The University of Texas, M.D. Anderson Cancer Center, 1515 Holcombe Blvd, Box 354, Houston, TX 77030, USA (YY, ZL, RZL, RCBJr) Published in Atlas Database: September 2009 Online updated version : http://AtlasGeneticsOncology.org/Genes/DIRAS3ID702ch1p31.html DOI: 10.4267/2042/44814 This article is an update of : Guénard F, Durocher F. DHX9 (DEAH (Asp-Glu-Ala-His) box polypeptide 9). Atlas Genet Cytogenet Oncol Haematol 2010;14(6):547-549 This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 2.0 France Licence. © 2010 Atlas of Genetics and Cytogenetics in Oncology and Haematology region consisting of 81 nucleotides, whereas the second Identity exon contains the entire protein-coding region. The two Other names: ARHI; NOEY2; RHOI exons are separated by an intron of 3.2 kb. There are HGNC (Hugo): DIRAS3 three CpG island regions. CPG island I (nucleotide (nt) -1232 to -914) is located about 1 kb upstream of the Location: 1p31.3 transcription initiation site; CpG island II (nt -206 to Local order: Telomeric to GNG12, RMU7-80P and +79) is near the transcription initiation region and centromeric to GPR177, RPS7P4. adjacent exon 1; CpG island III (nt +3343 to +3691) is Note: DIRAS3 is also known as NOEY2 and ARHI located in the protein-encoding region of exon 2. (Ras homologue member I). Transcription DNA/RNA The entire protein-coding region is located within exon 2 and encodes a 229-residue small GTP-binding Description protein.
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The Tumor-Suppressor Gene ARHI (DIRAS3) Suppresses Ovarian Cancer Cell Migration Through Inhibition of the Stat3 and FAK/Rho Signaling Pathways
Oncogene (2012) 31, 68–79 & 2012 Macmillan Publishers Limited All rights reserved 0950-9232/12 www.nature.com/onc ORIGINAL ARTICLE The tumor-suppressor gene ARHI (DIRAS3) suppresses ovarian cancer cell migration through inhibition of the Stat3 and FAK/Rho signaling pathways DB Badgwell1,3,ZLu1,3,KLe1, F Gao1, M Yang1, GK Suh1, J-J Bao1, P Das1, M Andreeff 2, W Chen1,YYu1, AA Ahmed1, W S-L Liao1 and RC Bast Jr1 1Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA and 2Department of Blood and Marrow Transplantation, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Ovarian cancers migrate and metastasize over the surface Keywords: tumor-suppressor gene ARHI; migration of the peritoneal cavity. Consequently, dysregulation of suppression; Stat3; RhoA GTPase; cytoskeleton mechanisms that limit cell migration may be particularly important in the pathogenesis of the disease. ARHI is an imprinted tumor-suppressor gene that is downregulated in 460% of ovarian cancers, and its loss is associated Introduction with decreased progression-free survival. ARHI encodes a 26-kDa GTPase with homology to Ras. In contrast Epithelial ovarian cancers have been thought to arise to Ras, ARHI inhibits cell growth, but whether it also from cells that cover the ovarian surface or that line sub- regulates cell motility has not been studied previously. serosal inclusion cysts. Recently, cancers that resemble Here we report that re-expression of ARHI decreases the ovarian primaries have been shown to arise from the motility of IL-6- and epidermal growth factor (EGF)- ﬁmbriae of the Fallopian tube, deposits of endometriosis stimulated SKOv3 and Hey ovarian cancer cells, inhibit- and from the peritoneal surface.
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The E3 Ligase TRIM32 Is an Effector of the RAS Family Gtpase RAP2
The E3 Ligase TRIM32 is an effector of the RAS family GTPase RAP2 Berna Demiray A thesis submitted towards the degree of Doctor of Philosophy Cancer Institute University College London 2014 Declaration I, Berna Demiray, confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated. London, 2014 The E3 Ligase TRIM32 is an Effector of the RAS family GTPase RAP2 Classical RAS oncogenes are mutated in approximately 30% of human tumours and RAP proteins are closely related to classical RAS proteins. RAP1 has an identical effector domain to RAS whereas RAP2 differs by one amino acid. RAP2 not only shares effectors with other classical RAS family members, but it also has its own specific effectors that do not bind to RAP1 or classical RAS family proteins. Thus, although closely related, RAP2 performs distinct functions, although these have been poorly characterised. Using RAP2 as bait in Tandem Affinity Purifications, we have identified several RAP2 interacting proteins including TRIM32; a protein implicated in diverse pathological processes such as Limb-Girdle Muscular Dystrophy (LGMD2H), and Bardet-Biedl syndrome (BBS). TRIM32 was shown to interact specifically with RAP2 in an activation- and effector domain-dependent manner; demonstrating stronger interaction with the RAP2 V12 mutant than the wild-type RAP2 and defective binding to the effector mutant RAP2 V12A38. The interaction was mapped to the C-terminus of TRIM32 (containing the NHL domains) while mutations found in LGMD2H (R394H, D487N, ∆588) were found to disrupt binding to RAP2. The TRIM32 P130S mutant linked to BBS did not affect binding to RAP2, suggesting that the RAP2-TRIM32 interaction may be functionally involved in LGMD2H.
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The Role of the DIRAS Family Members in Regulating Ras Function, Cancer Growth and Autophagy
The Texas Medical Center Library DigitalCommons@TMC The University of Texas MD Anderson Cancer Center UTHealth Graduate School of The University of Texas MD Anderson Cancer Biomedical Sciences Dissertations and Theses Center UTHealth Graduate School of (Open Access) Biomedical Sciences 5-2017 The Role of the DIRAS Family Members in Regulating Ras Function, Cancer Growth and Autophagy Margie Nicole Sutton Follow this and additional works at: https://digitalcommons.library.tmc.edu/utgsbs_dissertations Part of the Biology Commons, Cancer Biology Commons, Cell Biology Commons, Laboratory and Basic Science Research Commons, and the Medicine and Health Sciences Commons Recommended Citation Sutton, Margie Nicole, "The Role of the DIRAS Family Members in Regulating Ras Function, Cancer Growth and Autophagy" (2017). The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access). 741. https://digitalcommons.library.tmc.edu/utgsbs_dissertations/741 This Dissertation (PhD) is brought to you for free and open access by the The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences at DigitalCommons@TMC. It has been accepted for inclusion in The University of Texas MD Anderson Cancer Center UTHealth Graduate School of Biomedical Sciences Dissertations and Theses (Open Access) by an authorized administrator of DigitalCommons@TMC. For more information, please contact [email protected]. THE ROLE OF THE DIRAS FAMILY MEMBERS IN REGULATING RAS FUNCTION, CANCER GROWTH AND AUTOPHAGY by Margie Nicole Sutton, B.S. APPROVED: ______________________________ Robert C. Bast Jr., M.D. Advisory Professor ______________________________ George Calin, M.D, Ph.D. ______________________________ Gordon Mills, M.D., Ph.D.
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Re-Expression of ARHI (DIRAS3) Induces Autophagy in Breast Cancer Cells and Enhances the Inhibitory Effect of Paclitaxel
Zou et al. BMC Cancer 2011, 11:22 http://www.biomedcentral.com/1471-2407/11/22 RESEARCHARTICLE Open Access Re-expression of ARHI (DIRAS3) induces autophagy in breast cancer cells and enhances the inhibitory effect of paclitaxel Chun-Fang Zou1†, Luoqi Jia1†, Hongyan Jin1, Ming Yao2, Naiqing Zhao3, Jin Huan3, Zhen Lu4, Robert C Bast Jr4, Youji Feng1,5*, Yinhua Yu1,4* Abstract Background: ARHI is a Ras-related imprinted gene that inhibits cancer cell growth and motility. ARHI is downregulated in the majority of breast cancers, and loss of its expression is associated with its progression from ductal carcinoma in situ (DCIS) to invasive disease. In ovarian cancer, re-expression of ARHI induces autophagy and leads to autophagic death in cell culture; however, ARHI re-expression enables ovarian cancer cells to remain dormant when they are grown in mice as xenografts. The purpose of this study is to examine whether ARHI induces autophagy in breast cancer cells and to evaluate the effects of ARHI gene re-expression in combination with paclitaxel. Methods: Re-expression of ARHI was achieved by transfection, by treatment with trichostatin A (TSA) or by a combination of TSA and 5-aza-2’-deoxycytidine (DAC) in breast cancer cell cultures and by liposomal delivery of ARHI in breast tumor xenografts. Results: ARHI re-expression induces autophagy in breast cancer cells, and ARHI is essential for the induction of autophagy. When ARHI was re-expressed in breast cancer cells treated with paclitaxel, the growth inhibitory effect of paclitaxel was enhanced in both the cell culture and the xenografts.
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Trans-Fatty Acids Promote P53-Dependent Apoptosis Triggered by Cisplatin-Induced DNA Interstrand Crosslinks Via the Nox-RIP1-ASK
www.nature.com/scientificreports OPEN trans‑Fatty acids promote p53‑dependent apoptosis triggered by cisplatin‑induced DNA interstrand crosslinks via the Nox‑RIP1‑ASK1‑MAPK pathway Yusuke Hirata1,2, Miki Takahashi1,2, Yuto Yamada1,2, Ryosuke Matsui1, Aya Inoue1, Ryo Ashida1, Takuya Noguchi1 & Atsushi Matsuzawa1* trans‑Fatty acids (TFAs) are food‑derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro‑apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)‑inducing agent, via a non‑canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal‑regulating kinase (ASK1), a reactive oxygen species (ROS)‑responsive kinase. However, here we found that in the case of CDDP‑ induced apoptosis, EA‑mediated pro‑apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1‑p38/c‑Jun N‑terminal kinase (JNK) mitogen‑activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co‑treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor‑interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53‑dependent apoptosis through the enhancement of the Nox‑RIP1‑ASK1‑MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.
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