title: Cell fusion induced by ERVWE1 or measles virus causes cellular senescence.
abstract: Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers of cellular senescence. During embryonic development, ERVWE1-mediated cell fusion results in formation of the syncytiotrophoblast, which serves as the maternal/fetal interface at the placenta. Expression of ERVWE1 caused cell fusion in normal and cancer cells, leading to formation of hyperploid syncytia exhibiting features of cellular senescence. Infection by the measles virus, which leads to cell fusion, also induced cellular senescence in normal and cancer cells. The fused cells activated the main molecular pathways of senescence, the p53- and p16-pRb-dependent pathways; the senescence-associated secretory phenotype; and immune surveillance-related proteins. Thus, fusion-induced senescence might be needed for proper syncytiotrophoblast function during embryonic development, and reuse of this senescence program later in life protects against pathological expression of endogenous fusogens and fusogenic viral infections.
authors.affiliation: Department of Molecular Cell Biology, The Weizmann Institute of Science, Rehovot 76100, Israel;
authors.forename: Anna
authors.initials: A
authors.lastname: Chuprin
authors.forename: Hilah
authors.initials: H
authors.lastname: Gal
authors.forename: Tal
authors.initials: T
authors.lastname: Biron-Shental
authors.forename: Anat
authors.initials: A
authors.lastname: Biran
authors.forename: Aliza
authors.initials: A
authors.lastname: Amiel
authors.forename: Shmuel
authors.initials: S
authors.lastname: Rozenblatt
authors.forename: Valery
authors.initials: V
authors.lastname: Krizhanovsky
mesh_terms: D002459:Cell Fusion; D002460:Cell Line; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000235:genetics / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D015686:Gene Products, env / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008457:Measles / Q000503:physiopathology; D008459:Measles virus / Q000502:physiology*; D010920:Placenta / Q000166:cytology; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D015686:Gene Products, env; D011257:Pregnancy Proteins; C405335:syncytin
keywords: ERVWE1; cell fusion; cellular senescence; p53; pRb; placenta