Hsu Jenny, Sage Julien
a Departments of Pediatrics and Genetics , Stanford University , Stanford , CA , USA.
Cell Cycle. 2016 Dec;15(23):3183-3190. doi: 10.1080/15384101.2016.1234551. Epub 2016 Oct 18.
The E2F family of transcription factors is a key determinant of cell proliferation in response to extra- and intra-cellular signals. Within this family, E2F4 is a transcriptional repressor whose activity is critical to engage and maintain cell cycle arrest in G0/G1 in conjunction with members of the retinoblastoma (RB) family. However, recent observations challenge this paradigm and indicate that E2F4 has a multitude of functions in cells besides this cell cycle regulatory role, including in embryonic and adult stem cells, during regenerative processes, and in cancer. Some of these new functions are independent of the RB family and involve direct activation of target genes. Here we review the canonical functions of E2F4 and discuss recent evidence expanding the role of this transcription factor, with a focus on cell fate decisions in tissue homeostasis and regeneration.
转录因子E2F家族是细胞响应细胞外和细胞内信号进行增殖的关键决定因素。在这个家族中，E2F4是一种转录抑制因子，其活性对于与视网膜母细胞瘤（RB）家族成员协同作用使细胞周期停滞在G0/G1期至关重要。然而，最近的观察结果对这一模式提出了挑战，并表明E2F4除了这种细胞周期调节作用外，在细胞中还具有多种功能，包括在胚胎和成年干细胞中、再生过程中以及癌症中。其中一些新功能独立于RB家族，涉及靶基因的直接激活。在这里，我们回顾了E2F4的经典功能，并讨论了最近扩展该转录因子作用的证据，重点关注组织稳态和再生中的细胞命运决定。
