结合p60c-src与多瘤病毒中T抗原废除线粒分裂特异激活的相关性
Nature
|April 4, 1991
概括
多细胞瘤中T抗原激活p60c-src氨酸激酶,在整个细胞周期中保持高活性. 这绕过了正常的细胞循环调节,与自然发生的SRC激酶的线粒激活不同.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 病毒学 病毒学
- 在瘤学瘤学.
背景情况:
- 多瘤中T抗原对于动物瘤发生和病毒细胞转化至关重要.
- 中T抗原与细胞氨酸激酶p60c-src结合并激活它.
- p60c-src活动通常由细胞周期调节,在线粒分裂期间达到峰值.
研究的目的:
- 研究多瘤中T抗原对p60c-src活动调节的影响.
- 要确定中T抗原是否会改变p60c-src.src的细胞周期特定调节.
- 为了比较中T-激活的src酶与瘤致癌突变的活性.
主要方法:
- 在表达中T抗原的细胞中,分析了p60c-src在氨酸527和416的酸化状态.
- 检测不同细胞循环阶段 (线粒分裂和中间阶段) 中的SRC激酶活性,在中T的存在下.
- 在表达致癌性p60c-src(527F) 突变的细胞中评估src激酶活性.
主要成果:
- 线性p60c-src在氨酸527处脱,与已知的调节一致.
- 表达中型T抗原的细胞在线分裂和介质阶段都表现出高的SRC激酶活性.
- 致癌的p60c-src(527F) 突变体在所有细胞周期阶段都表现出高活性.
结论:
- 多细胞瘤中T抗原破坏了p60c-src的正常细胞周期依赖的抑制.
- 中T抗原保持高的SRC激酶活性,独立于细胞周期阶段.
- 这种由中T抗原持续激活有助于其致癌潜力.
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