{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T22:11:33Z","timestamp":1774476693750,"version":"3.50.1"},"reference-count":94,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,11,2]],"date-time":"2022-11-02T00:00:00Z","timestamp":1667347200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>An increasing body of evidence in recent years supports an association of the betaretrovirus mouse mammary tumor virus (MMTV) with human breast cancer. This is an issue that still raises heated controversy. We have come to address this association using the signal peptide p14 of the MMTV envelope precursor protein as a key element of our strategy. In addition to its signal peptide function, p14 has some significant post endoplasmic reticulum (ER)-targeting characteristics: (1) it localizes to nucleoli where it binds key proteins (RPL5 and B23) involved (among other activities) in the regulation of nucleolar stress response, ribosome biogenesis and p53 stabilization; (2) p14 is a nuclear export factor; (3) it is expressed on the cell surface of infected cells, and as such, is amenable to, and successfully used, in preventive vaccination against experimental tumors that harbor MMTV; (4) the growth of such tumors is impaired in vivo using a combination of monoclonal anti-p14 antibodies or adoptive T-cell transfer treatments; (5) p14 is a phospho-protein endogenously phosphorylated by two different serine kinases. The phosphorylation status of the two sites determines whether p14 will function in an oncogenic or tumor-suppressing capacity; (6) transcriptional activation of genes (RPL5, ErbB4) correlates with the oncogenic potential of MMTV; (7) finally, polyclonal anti-p14 antibodies have been applied in immune histochemistry analyses of breast cancer cases using formalin fixed paraffin-embedded sections, supporting the associations of MMTV with the disease. Taken together, the above findings constitute a road map towards the diagnosis and possible prevention and treatment of MMTV-associated breast cancer.<\/jats:p>","DOI":"10.3390\/v14112435","type":"journal-article","created":{"date-parts":[[2022,11,3]],"date-time":"2022-11-03T04:11:31Z","timestamp":1667448691000},"page":"2435","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Life after Cleavage: The Story of a \u03b2-Retroviral (MMTV) Signal Peptide\u2014From Murine Lymphoma to Human Breast Cancer"],"prefix":"10.3390","volume":"14","author":[{"given":"Jacob","family":"Hochman","sequence":"first","affiliation":[{"name":"Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7261-2549","authenticated-orcid":false,"given":"Ori","family":"Braitbard","sequence":"additional","affiliation":[{"name":"Department of Cell and Developmental Biology, Alexander Silberman Institute of Life Science, The Hebrew University of Jerusalem, Jerusalem 9190401, Israel"},{"name":"Department of Bioinformatics, The Faculty of Life and Health Sciences, Jerusalem College of Technology, Jerusalem 9372115, Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1016\/j.canlet.2010.09.011","article-title":"Viruses and human cancer: From detection to causality","volume":"305","author":"Sarid","year":"2011","journal-title":"Cancer Lett."},{"key":"ref_2","first-page":"1038","article-title":"Mammary cancer in mice of different ages and stocks following the administration of the mammary tumor agent","volume":"16","author":"Bitnner","year":"1956","journal-title":"Cancer Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1128\/jvi.43.3.819-829.1982","article-title":"Acquisition of proviral DNA of mouse mammary tumor virus in thymic leukemia cells from GR mice","volume":"43","author":"Michalides","year":"1982","journal-title":"J. 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