E4F蛋白在胚胎细胞周期的有丝分裂进程中是必需的。
The E4F protein is required for mitotic progression during embryonic cell cycles.
作者信息
Le Cam Laurent, Lacroix Matthieu, Ciemerych Maria A, Sardet Claude, Sicinski Piotr
机构信息
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
出版信息
Mol Cell Biol. 2004 Jul;24(14):6467-75. doi: 10.1128/MCB.24.14.6467-6475.2004.
Abstract
The ubiquitously expressed E4F protein was originally identified as an E1A-regulated cellular transcription factor required for adenovirus replication. The function of this protein in normal cell physiology remains largely unknown. To address this issue, we generated E4F knockout mice by gene targeting. Embryos lacking E4F die at the peri-implantation stage, while in vitro-cultured E4F(-/-) blastocysts exhibit defects in mitotic progression, chromosomal missegregation, and increased apoptosis. Consistent with these observations, we found that E4F localizes to the mitotic spindle during the M phase of early embryos. Our results establish a crucial role for E4F during early embryonic cell cycles and reveal an unexpected function for E4F in mitosis.
摘要
广泛表达的E4F蛋白最初被鉴定为腺病毒复制所需的E1A调节细胞转录因子。该蛋白在正常细胞生理学中的功能在很大程度上仍然未知。为了解决这个问题，我们通过基因靶向生成了E4F基因敲除小鼠。缺乏E4F的胚胎在植入前阶段死亡，而体外培养的E4F(-/-)囊胚在有丝分裂进程、染色体错分离和细胞凋亡增加方面表现出缺陷。与这些观察结果一致，我们发现E4F在早期胚胎的M期定位于有丝分裂纺锤体。我们的结果确立了E4F在早期胚胎细胞周期中的关键作用，并揭示了E4F在有丝分裂中的意外功能。
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