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IBGM"],"award-info":[{"award-number":["CL-EI-2021 IBGM"]}]},{"name":"\u201cMargarita Salas\u201d Program from the Spanish Ministry of Universities","award":["AMMICa US23"],"award-info":[{"award-number":["AMMICa US23"]}]},{"name":"\u201cMargarita Salas\u201d Program from the Spanish Ministry of Universities","award":["CNRS UMS3655"],"award-info":[{"award-number":["CNRS UMS3655"]}]},{"name":"\u201cMargarita Salas\u201d Program from the Spanish Ministry of Universities","award":["ANR-18-IDEX-0001"],"award-info":[{"award-number":["ANR-18-IDEX-0001"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The B-cell lymphoma 2 (Bcl-2) family of proteins is the main regulator of apoptosis. However, multiple emerging evidence has revealed that Bcl-2 family proteins are also involved in cellular senescence. On the one hand, the different expression of these proteins determines the entry into senescence. On the other hand, entry into senescence modulates the expression of these proteins, generally conferring resistance to apoptosis. With some exceptions, senescent cells are characterized by the upregulation of antiapoptotic proteins and downregulation of proapoptotic proteins. Under physiological conditions, freshly formed tetraploid cells die by apoptosis due to the tetraploidy checkpoint. However, suppression of Bcl-2 associated x protein (Bax), as well as overexpression of Bcl-2, favors the appearance and survival of tetraploid cells. Furthermore, it is noteworthy that our laboratory has shown that the joint absence of Bax and Bcl-2 antagonist\/killer (Bak) favors the entry into senescence of tetraploid cells. Certain microtubule inhibitory chemotherapies, such as taxanes and vinca alkaloids, induce the generation of tetraploid cells. Moreover, the combined use of inhibitors of antiapoptotic proteins of the Bcl-2 family with microtubule inhibitors increases their efficacy. In this review, we aim to shed light on the involvement of the Bcl-2 family of proteins in the senescence program activated after tetraploidization and the possibility of using this knowledge to create a new therapeutic strategy targeting cancer cells.<\/jats:p>","DOI":"10.3390\/ijms24076374","type":"journal-article","created":{"date-parts":[[2023,3,29]],"date-time":"2023-03-29T02:03:53Z","timestamp":1680055433000},"page":"6374","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Involvement of Bcl-2 Family Proteins in Tetraploidization-Related Senescence"],"prefix":"10.3390","volume":"24","author":[{"given":"Daniel","family":"Barriuso","sequence":"first","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid\u2014CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5663-3518","authenticated-orcid":false,"given":"Lucia","family":"Alvarez-Frutos","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid\u2014CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucia","family":"Gonzalez-Gutierrez","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid\u2014CSIC, 47003 Valladolid, Spain"},{"name":"Centre de Recherche des Cordeliers, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Inserm U1138, Institut Universitaire de France, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Omar","family":"Moti\u00f1o","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Inserm U1138, Institut Universitaire de France, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9334-4405","authenticated-orcid":false,"given":"Guido","family":"Kroemer","sequence":"additional","affiliation":[{"name":"Centre de Recherche des Cordeliers, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Inserm U1138, Institut Universitaire de France, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"},{"name":"Institut du Cancer Paris CARPEM, Department of Biology, H\u00f4pital Europ\u00e9en Georges Pompidou, AP-HP, 75015 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Palacios-Ramirez","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid\u2014CSIC, 47003 Valladolid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6887-2436","authenticated-orcid":false,"given":"Laura","family":"Senovilla","sequence":"additional","affiliation":[{"name":"Unidad de Excelencia Instituto de Biolog\u00eda y Gen\u00e9tica Molecular (IBGM), Universidad de Valladolid\u2014CSIC, 47003 Valladolid, Spain"},{"name":"Centre de Recherche des Cordeliers, Equipe Labellis\u00e9e par la Ligue Contre le Cancer, Inserm U1138, Institut Universitaire de France, Universit\u00e9 Paris Cit\u00e9, Sorbonne Universit\u00e9, 75006 Paris, France"},{"name":"Metabolomics and Cell Biology Platforms, Institut Gustave Roussy, 94805 Villejuif, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.tcb.2020.03.004","article-title":"Noncanonical Cell Fate Regulation by Bcl-2 Proteins","volume":"30","author":"Chong","year":"2020","journal-title":"Trends Cell Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107943","DOI":"10.1016\/j.pharmthera.2021.107943","article-title":"The interplay between apoptosis and cellular senescence: Bcl-2 family proteins as targets for cancer therapy","volume":"230","author":"Basu","year":"2022","journal-title":"Pharmacol. 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