title: The presence of 19-kDa Bcl-2 in dividing cells.
abstract: The 26-kDa bcl-2 gene product inhibits apoptosis and cell proliferation. Cleavage of Bcl-2 into a 22-kDa fragment inactivates its anti-apoptotic activity and is a key event in apoptosis. Here, and in recent work, we describe massive 19-kDa Bcl-2 immunoreactivity in non-apoptotic cells, suggesting a link with viability rather than cell death. Loss of 19 kDa Bcl-2 in adriamycin-induced apoptotic cells underlines this. G2/M-phase accumulation of cells by nocodazole-treatment also results in loss of 19 kDa Bcl-2. Next to its well-documented cytoplasmic localization, a substantial pool of Bcl-2 resides in nuclei. Hampered nuclear localization of Bcl-2 leads to a loss of cell cycle repression. This has led us to point at a pivotal role for nuclear Bcl-2 in cellular proliferation. In this report, cellular fractionation of bcl-2 transfected cells in various phases of the cell cycle reveals a constitutive cytoplasmic pool of 19 kDa Bcl-2. Nuclear 19-kDa Bcl-2 immunoreactivity is far more pronounced in rapidly dividing nuclei compared with more quiescent nuclear fractions. This implicates that ongoing cell proliferation involves cleavage of nuclear Bcl-2 with a 19-kDa fragment.
authors.affiliation: Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands. Rob.W.Hoetelmans@GSK.com
authors.forename: R W M
authors.initials: RW
authors.lastname: Hoetelmans
authors.forename: C J H
authors.initials: CJ
authors.lastname: Van de Velde
authors.forename: J H
authors.initials: JH
authors.lastname: Van Dierendonck
mesh_terms: D000818:Animals; D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D002458:Cell Fractionation; D002467:Cell Nucleus / Q000378:metabolism*; D004317:Doxorubicin / Q000494:pharmacology; D019254:Genes, bcl-2; D006801:Humans; D015739:Nocodazole / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D004317:Doxorubicin; D015739:Nocodazole