{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T09:15:46Z","timestamp":1778404546289,"version":"3.51.4"},"reference-count":24,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T00:00:00Z","timestamp":1643932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A22903"],"award-info":[{"award-number":["A22903"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["A31287"],"award-info":[{"award-number":["A31287"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:p>\n                    Macroautophagy is a membrane\u2010trafficking process that delivers cytoplasmic material to lysosomes for degradation. The process preserves cellular integrity by removing damaged cellular constituents and can promote cell survival by providing substrates for energy production during hiatuses of nutrient availability. The process is also highly responsive to other forms of cellular stress. For example, DNA damage can induce autophagy and this involves up\u2010regulation of the Damage\u2010Regulated Autophagy Modulator\u20101 (DRAM\u20101) by the tumor suppressor p53. DRAM\u20101 belongs to an evolutionarily conserved protein family, which has five members in humans and we describe here the initial characterization of two members of this family, which we term DRAM\u20104 and DRAM\u20105 for DRAM\u2010Related\/Associated Member 4\/5. We show that the genes encoding these proteins are not regulated by p53, but instead are induced by nutrient deprivation. Similar to other DRAM family proteins, however, DRAM\u20104 principally localizes to endosomes and DRAM\u20105 to the plasma membrane and both modulate autophagy flux when over\u2010expressed. Deletion of\n                    <jats:italic>DRAM\u20104<\/jats:italic>\n                    using CRISPR\/Cas\u20109 also increased autophagy flux, but we found that\n                    <jats:italic>DRAM\u20104<\/jats:italic>\n                    and\n                    <jats:italic>DRAM\u20105<\/jats:italic>\n                    undergo compensatory regulation, such that deletion of\n                    <jats:italic>DRAM\u20104<\/jats:italic>\n                    does not affect autophagy flux in the absence of DRAM\u20105. Similarly, deletion of\n                    <jats:italic>DRAM\u20104<\/jats:italic>\n                    also promotes cell survival following growth of cells in the absence of amino acids, serum, or glucose, but this effect is also impacted by the absence of DRAM\u20105. In summary, DRAM\u20104 and DRAM\u20105 are nutrient\u2010responsive members of the DRAM family that exhibit interconnected roles in the regulation of autophagy and cell survival under nutrient\u2010deprived conditions.\n                  <\/jats:p>","DOI":"10.1111\/febs.16365","type":"journal-article","created":{"date-parts":[[2022,1,21]],"date-time":"2022-01-21T04:34:36Z","timestamp":1642739676000},"page":"3752-3769","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["DRAM\u20104 and DRAM\u20105 are compensatory regulators of autophagy and cell survival in nutrient\u2010deprived conditions"],"prefix":"10.1111","volume":"289","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5396-3594","authenticated-orcid":false,"given":"Valentin J. A.","family":"Barthet","sequence":"first","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"},{"name":"Institute of Cancer Sciences University of Glasgow  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michaela","family":"Mrschtik","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elzbieta","family":"Kania","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"},{"name":"Institute of Cancer Sciences University of Glasgow  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0353-6532","authenticated-orcid":false,"given":"David G.","family":"McEwan","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Croft","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"O'Prey","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6644-542X","authenticated-orcid":false,"given":"Jaclyn S.","family":"Long","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1059-9681","authenticated-orcid":false,"given":"Kevin M.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Cancer Research UK Beatson Institute  Glasgow UK"},{"name":"Institute of Cancer Sciences University of Glasgow  UK"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,2,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-018-0092-5"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.3595"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2019.12.001"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2018.09.048"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.126128"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1042\/bse0550051"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.119.2.301"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature03029"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2006.05.034"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2019.07.021"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chom.2014.05.005"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.4161\/cc.8.14.9050"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1167\/iovs.15-17604"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.04.006"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11033-011-0835-x"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/cdd.2015.26"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2016.05.029"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.15252\/embr.201439151"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/35009130"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1209580"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1231143"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.mie.2016.09.076"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.abf9141"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature12865"}],"container-title":["The FEBS Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.16365","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/febs.16365","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/febs.16365","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,24]],"date-time":"2023-08-24T08:54:49Z","timestamp":1692867289000},"score":1,"resource":{"primary":{"URL":"https:\/\/febs.onlinelibrary.wiley.com\/doi\/10.1111\/febs.16365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,4]]},"references-count":24,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["10.1111\/febs.16365"],"URL":"https:\/\/doi.org\/10.1111\/febs.16365","archive":["Portico"],"relation":{"has-review":[{"id-type":"doi","id":"10.1111\/FEBS.16365\/v1\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v2\/review2","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v2\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v2\/response1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v2\/decision1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v1\/review1","asserted-by":"object"},{"id-type":"doi","id":"10.1111\/FEBS.16365\/v1\/review2","asserted-by":"object"}]},"ISSN":["1742-464X","1742-4658"],"issn-type":[{"value":"1742-464X","type":"print"},{"value":"1742-4658","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,4]]},"assertion":[{"value":"2021-08-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-01-19","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-04","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}