Changes in p19Arf localization accompany apoptotic crisis during pre-B-cell transformation by Abelson murine leukemia virus.
Changes in p19Arf localization accompany apoptotic crisis during pre-B-cell transformation by Abelson murine leukemia virus.
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在 Abelson 鼠白血病病毒的前 B 细胞转化过程中，p19Arf 定位的变化伴随着细胞凋亡危机。
DOI：
10.1128/jvi.00348-08
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发表时间：
2008
影响因子：
5.4
通讯作者：
Rosenberg,Naomi
中科院分区：
文献类型：
--
作者：
Zimmerman,RebekahStackpole;Rosenberg,Naomi
Abelson鼠白血病病毒（Ab-MLV）的转化是一个多步骤的过程，其中来自v-Abl癌蛋白的生长刺激信号和来自p19 Arf-p53肿瘤抑制途径的生长抑制信号彼此对抗并影响感染的结果。该过程涉及一个增殖阶段，在此期间，高活力的初级转化体扩增，随后是一个明显的凋亡期（称为“危机”），这取决于p19 Arf和p53的存在;在此阶段存活的罕见细胞出现完全转化和恶性。为了了解v-Abl表达影响p19 Arf表达的方式，我们检测了在Ab-MLV转化过程的所有阶段Arf表达的变化。与v-Abl刺激Myc的能力一致，Myc是已知诱导p19 Arf的转录因子，MycandArfare在感染后不久被诱导并表达p19 Arfis。在这些早期时间点，感染的细胞保持高度活力。危机的发生以p19 Arf表达的增加和蛋白质从核质到核仁的定位变化为标志。这些数据共同表明，p19 Arf的定位和表达水平调节蛋白质在肿瘤发生过程中的作用，并揭示了p19 Arf介导的反应受到多层调控，影响其在Ab-MLV介导的转化过程中的功能。
Transformation by Abelson murine leukemia virus (Ab-MLV) is a multistep process in which growth-stimulatory signals from the v-Abl oncoprotein and growth-suppressive signals from the p19Arf-p53 tumor suppressor pathway oppose each other and influence the outcome of infection. The process involves a proliferative phase during which highly viable primary transformants expand, followed by a period of marked apoptosis (called “crisis”) that is dependent on the presence of p19Arfand p53; rare cells that survive this phase emerge as fully transformed and malignant. To understand the way in which v-Abl expression affects p19Arfexpression, we examined changes in expression ofArfduring all stages of Ab-MLV transformation process. As is consistent with the ability of v-Abl to stimulate Myc, a transcription factor known to induce p19Arf,MycandArfare induced soon after infection and p19Arfis expressed. At these early time points, the infected cells remain highly viable. The onset of crisis is marked by an increase in p19Arfexpression and a change in localization of the protein from the nucleoplasm to the nucleolus. These data together suggest that the localization and expression levels of p19Arfmodulate the effects of the protein during oncogenesis and reveal that the p19Arf-mediated response is subject to multiple layers of regulation that influence its function during Ab-MLV-mediated transformation.