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We previously reported that E4F1 is essential for the survival of murine p53-deficient cancer cells by controlling the expression of genes involved in mitochondria functions and metabolism, and in cell-cycle checkpoints, including CHEK1, a major component of the DNA damage and replication stress responses. Here, combining ChIP-Seq and RNA-Seq approaches, we identified the transcriptional program directly controlled by E4F1 in Human Triple-Negative Breast Cancer cells (TNBC). E4F1 binds and regulates a limited list of direct target genes (57 genes) in these cells, including the human CHEK1 gene and, surprisingly, also two other genes encoding post-transcriptional regulators of the ATM\/ATR-CHK1 axis, namely, the TTT complex component TTI2 and the phosphatase PPP5C, that are essential for the folding and stability, and the signaling of ATM\/ATR kinases, respectively. Importantly, E4F1 also binds the promoter of these genes in vivo in Primary Derived Xenograft (PDX) of human TNBC. Consequently, the protein levels and signaling of CHK1 but also of ATM\/ATR kinases are strongly downregulated in E4F1-depleted TNBC cells resulting in a deficiency of the DNA damage and replicative stress response in these cells. The E4F1-depleted cells fail to arrest into S-phase upon treatment with the replication-stalling agent Gemcitabine, and are highly sensitized to this drug, as well as to other DNA-damaging agents, such as Cisplatin. Altogether, our data indicate that in breast cancer cells the ATM\/ATR-CHK1 signaling pathway and DNA damage-stress response are tightly controlled at the transcriptional and post-transcriptional level by E4F1.<\/jats:p>","DOI":"10.3390\/ijms23169217","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T23:44:25Z","timestamp":1660693465000},"page":"9217","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Multi-Level Control of the ATM\/ATR-CHK1 Axis by the Transcription Factor E4F1 in Triple-Negative Breast Cancer"],"prefix":"10.3390","volume":"23","author":[{"given":"Kalil","family":"Batnini","sequence":"first","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9299-744X","authenticated-orcid":false,"given":"Thibault","family":"Houles","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6200-5681","authenticated-orcid":false,"given":"Olivier","family":"Kirsh","sequence":"additional","affiliation":[{"name":"Epigenetics and Cell Fate Team, CNRS, University Paris Cit\u00e9, 75006 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2200-2651","authenticated-orcid":false,"given":"Stanislas","family":"Du Manoir","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Zaroual","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H\u00e9l\u00e8ne","family":"Delpech","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chlo\u00e9","family":"Fallet","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1268-9058","authenticated-orcid":false,"given":"Matthieu","family":"Lacroix","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0325-878X","authenticated-orcid":false,"given":"Laurent","family":"Le Cam","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 Montpellier, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Theillet","sequence":"additional","affiliation":[{"name":"Institut de Recherche en Canc\u00e9rologie de Montpellier, IRCM U1194, Montpellier University, INSERM, ICM, CNRS, 34090 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vitro","volume":"6","author":"Lee","year":"1987","journal-title":"EMBO J."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4073","DOI":"10.1002\/j.1460-2075.1987.tb02753.x","article-title":"Identification of an E1A-inducible cellular factor that interacts with regulatory sequences within the adenovirus E4 promoter","volume":"6","author":"Raychaudhuri","year":"1987","journal-title":"EMBO J."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"7738","DOI":"10.1073\/pnas.130198397","article-title":"pRB binds to and modulates the transrepressing activity of the E1A-regulated transcription factor p120E4F","volume":"97","author":"Fajas","year":"2000","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1074\/jbc.M210978200","article-title":"Association of p14ARF with the p120E4F transcriptional repressor enhances cell cycle inhibition","volume":"278","author":"Rizos","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1038\/sj.onc.1203250","article-title":"p53 is involved in the p120E4F-mediated growth arrest","volume":"19","author":"Sandy","year":"2000","journal-title":"Oncogene"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1158\/0008-5472.CAN-03-2622","article-title":"Identification of the E1A-regulated transcription factor p120 E4F as an interacting partner of the RASSF1A candidate tumor suppressor gene","volume":"64","author":"Fenton","year":"2004","journal-title":"Cancer Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1101\/gad.1453406","article-title":"E4F1: A novel candidate factor for mediating BMI1 function in primitive hematopoietic cells","volume":"20","author":"Chagraoui","year":"2006","journal-title":"Genes Dev."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2006.09.031","article-title":"E4F1 is an atypical ubiquitin ligase that modulates p53 effector functions independently of degradation","volume":"127","author":"Linares","year":"2006","journal-title":"Cell"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"5475","DOI":"10.1038\/sj.onc.1209567","article-title":"The LIM-only protein FHL2 is a negative regulator of E4F1","volume":"25","author":"Paul","year":"2006","journal-title":"Oncogene"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.celrep.2015.03.019","article-title":"E4F1 is a master regulator of CHK1-mediated functions","volume":"11","author":"Grote","year":"2015","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e2019408118","DOI":"10.1073\/pnas.2019408118","article-title":"Zinc finger protein E4F1 cooperates with PARP1 and BRG1 to promote DNA double-trand break repair","volume":"118","author":"Moison","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"6467","DOI":"10.1128\/MCB.24.14.6467-6475.2004","article-title":"The E4F protein is required for mitotic progression during embryonic cell cycles","volume":"24","author":"Lacroix","year":"2004","journal-title":"Mol. Cell. Biol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"21076","DOI":"10.1073\/pnas.1010167107","article-title":"Transcription factor E4F1 is essential for epidermal stem cell maintenance and skin homeostasis","volume":"107","author":"Lacroix","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Yan, R.G., Yang, Q.L., and Yang, Q.E. (2020). E4 Transcription Factor 1 (E4F1) Regulates Sertoli Cell Proliferation and Fertility in Mice. Animals, 10.","DOI":"10.3390\/ani10091691"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1403","DOI":"10.1084\/jem.20101995","article-title":"E4F1 deficiency results in oxidative stress-mediated cell death of leukemic cells","volume":"208","author":"Hatchi","year":"2011","journal-title":"J. Exp. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e22269","DOI":"10.1002\/jbt.22269","article-title":"E4F1 silencing inhibits the cell growth through cell-cycle arrest in malignant transformed cells induced by hydroquinone","volume":"33","author":"Tan","year":"2019","journal-title":"J. Biochem. Mol. Toxicol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1016\/j.celrep.2015.03.024","article-title":"The Transcription Factor E4F1 Coordinates CHK1-Dependent Checkpoint and Mitochondrial Functions","volume":"11","author":"Rodier","year":"2015","journal-title":"Cell Rep."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.gdata.2015.07.004","article-title":"Description of an optimized ChIP-seq analysis pipeline dedicated to genome wide identification of E4F1 binding sites in primary and transformed MEFs","volume":"5","author":"Rodier","year":"2015","journal-title":"Genomics Data"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"10998","DOI":"10.1073\/pnas.1602754113","article-title":"E4F1 controls a transcriptional program essential for pyruvate dehydrogenase activity","volume":"113","author":"Lacroix","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"11004","DOI":"10.1073\/pnas.1602751113","article-title":"E4F1-mediated control of pyruvate dehydrogenase activity is essential for skin homeostasis","volume":"113","author":"Seyran","year":"2016","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7037","DOI":"10.1038\/s41467-021-27307-3","article-title":"The multifunctional protein E4F1 links P53 to lipid metabolism in adipocytes","volume":"12","author":"Lacroix","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95206","DOI":"10.18632\/oncotarget.19199","article-title":"Checkpoint kinase 1 inhibitor sensitises transformed cells to dihydroorotate dehydrogenase inhibition","volume":"8","author":"Arnould","year":"2017","journal-title":"Oncotarget"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3681","DOI":"10.1111\/febs.13387","article-title":"DNA damage control: Regulation and functions of checkpoint kinase 1","volume":"282","author":"Smits","year":"2015","journal-title":"FEBS J."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1038\/s41571-018-0114-z","article-title":"State-of-the-art strategies for targeting the DNA damage response in cancer","volume":"16","author":"Tang","year":"2019","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e1012976","DOI":"10.1080\/23723556.2015.1012976","article-title":"Trial Watch: Targeting ATM-CHK2 and ATR-CHK1 pathways for anticancer therapy","volume":"2","author":"Manic","year":"2015","journal-title":"Mol. Cell. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Gorecki, L., Andrs, M., and Korabecny, J. (2021). Clinical Candidates Targeting the ATR-CHK1-WEE1 Axis in Cancer. Cancers, 13.","DOI":"10.3390\/cancers13040795"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"188521","DOI":"10.1016\/j.bbcan.2021.188521","article-title":"DNA damage response inhibitors: An avenue for TNBC treatment","volume":"1875","author":"Jin","year":"2021","journal-title":"Biochim. Biophys. Acta. Ver. Cancer"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Choi, W., and Lee, E.S. (2022). Therapeutic Targeting of DNA Damage Response in Cancer. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23031701"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.1038\/sj.emboj.7601666","article-title":"FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway","volume":"26","author":"Ling","year":"2007","journal-title":"EMBO J."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1016\/j.molcel.2016.11.005","article-title":"Mechanism of Ubiquitination and Deubiquitination in the Fanconi Anemia Pathway","volume":"65","author":"Murphy","year":"2017","journal-title":"Mol. Cell."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Akamatsu, Y., and Jasin, M. (2010). Role for the mammalian Swi5-Sfr1 complex in DNA strand break repair through homologous recombination. PLoS Genet., 6.","DOI":"10.1371\/journal.pgen.1001160"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6242","DOI":"10.1093\/nar\/gkw375","article-title":"Role of the RAD51-SWI5-SFR1 Ensemble in homologous recombination","volume":"44","author":"Su","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Feng, Y., Singleton, D., Guo, C., Gardner, A., Pakala, S., Kumar, R., Jensen, E., Zhang, J., and Khan, S. (2013). DNA homologous recombination factor SFR1 physically and functionally interacts with estrogen receptor alpha. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0068075"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1080\/10409238.2017.1394265","article-title":"Specificity of reversible ADP-ribosylation and regulation of cellular processes","volume":"53","author":"Crawford","year":"2018","journal-title":"Crit. Rev. Biochem. Mol. Biol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5045","DOI":"10.1093\/nar\/gkr099","article-title":"PARG is recruited to DNA damage sites through poly(ADP-ribose)- and PCNA-dependent mechanisms","volume":"39","author":"Mortusewicz","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1101\/gad.1176004","article-title":"Requirement of protein phosphatase 5 in DNA-damage-induced ATM activation","volume":"18","author":"Ali","year":"2004","journal-title":"Genes Dev."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"9910","DOI":"10.1128\/MCB.25.22.9910-9919.2005","article-title":"Protein phosphatase 5 is required for ATR-mediated checkpoint activation","volume":"25","author":"Zhang","year":"2005","journal-title":"Mol. Cell. Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"40413","DOI":"10.1074\/jbc.M111.244053","article-title":"Disruption of serine\/threonine protein phosphatase 5 (PP5:PPP5c) in mice reveals a novel role for PP5 in the regulation of ultraviolet light-induced phosphorylation of serine\/threonine protein kinase Chk1 (CHEK1)","volume":"286","author":"Amable","year":"2011","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1007\/s00294-018-0817-9","article-title":"Branching the Tel2 pathway for exact fit on phosphatidylinositol 3-kinase-related kinases","volume":"64","author":"Sugimoto","year":"2018","journal-title":"Curr. Genet."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"109867","DOI":"10.1016\/j.celrep.2021.109867","article-title":"The Hsp90 cochaperone TTT promotes cotranslational maturation of PIKKs prior to complex assembly","volume":"37","author":"Toullec","year":"2021","journal-title":"Cell Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1939","DOI":"10.1101\/gad.1934210","article-title":"A genetic screen identifies the Triple T complex required for DNA damage signaling and ATM and ATR stability","volume":"24","author":"Hurov","year":"2010","journal-title":"Genes Dev."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1016\/j.cell.2007.10.052","article-title":"Tel2 regulates the stability of PI3K-related protein kinases","volume":"131","author":"Takai","year":"2007","journal-title":"Cell"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2019","DOI":"10.1101\/gad.1956410","article-title":"Tel2 structure and function in the Hsp90-dependent maturation of mTOR and ATR complexes","volume":"24","author":"Takai","year":"2010","journal-title":"Genes Dev."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/j.molonc.2013.11.010","article-title":"Breast tumor PDXs are genetically plastic and correspond to a subset of aggressive cancers prone to relapse","volume":"8","author":"Orsetti","year":"2014","journal-title":"Mol. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1998","DOI":"10.1080\/15548627.2020.1805860","article-title":"ATM loss disrupts the autophagy-lysosomal pathway","volume":"17","author":"Cheng","year":"2021","journal-title":"Autophagy"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Rawlinson, R., and Massey, A.J. (2014). \u03b3H2AX and Chk1 phosphorylation as predictive pharmacodynamic biomarkers of Chk1 inhibitor-chemotherapy combination treatments. BMC. Cancer, 144.","DOI":"10.1186\/1471-2407-14-483"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"793884","DOI":"10.3389\/fgene.2022.793884","article-title":"Immediate-Early, Early, and Late Responses to DNA Double Stranded Breaks","volume":"13","author":"Kieffer","year":"2022","journal-title":"Front Genet."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"2806","DOI":"10.1158\/1078-0432.CCR-16-1316","article-title":"Therapeutic Activity of Anti-AXL Antibody against Triple-Negative Breast Cancer Patient-Derived Xenografts and Metastasis","volume":"23","author":"Leconet","year":"2017","journal-title":"Clin. Cancer Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9217\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:10:43Z","timestamp":1760141443000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/16\/9217"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,8,16]]},"references-count":48,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["ijms23169217"],"URL":"https:\/\/doi.org\/10.3390\/ijms23169217","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,8,16]]}}}