Hoetelmans R W M, Van de Velde C J H, Van Dierendonck J H
Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
Cell Prolif. 2003 Dec;36(6):293-306. doi: 10.1046/j.1365-2184.2003.00286.x.
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.
26 kDa的bcl - 2基因产物可抑制细胞凋亡和细胞增殖。Bcl - 2裂解为22 kDa的片段会使其抗凋亡活性失活，这是细胞凋亡中的关键事件。在此以及近期的研究中，我们描述了非凋亡细胞中大量存在的19 kDa Bcl - 2免疫反应性，这表明其与细胞活力而非细胞死亡有关。阿霉素诱导的凋亡细胞中19 kDa Bcl - 2的缺失强调了这一点。用诺考达唑处理使细胞在G2/M期积累也会导致19 kDa Bcl - 2的缺失。除了其已被充分证明的细胞质定位外，大量的Bcl - 2存在于细胞核中。Bcl - 2的核定位受阻会导致细胞周期抑制的丧失。这使我们指出核Bcl - 2在细胞增殖中起关键作用。在本报告中，对处于细胞周期不同阶段的bcl - 2转染细胞进行细胞分级分离，发现存在一个组成性的19 kDa Bcl - 2细胞质池。与更静止的核部分相比，快速分裂的细胞核中19 kDa Bcl - 2的免疫反应性要明显得多。这意味着正在进行的细胞增殖涉及核Bcl - 2裂解为19 kDa的片段。
