E2F4 is exported from the nucleus in a CRM1-dependent manner
E2F4 is exported from the nucleus in a CRM1-dependent manner
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DOI：
10.1128/mcb.21.4.1384-1392.2001
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发表时间：
2001-02-01
影响因子：
5.3
通讯作者：
Livingston, DM
中科院分区：
文献类型：
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作者：
Gaubatz, S;Lees, JA;Livingston, DM
E2F是一个转录因子家族，它是正常细胞周期控制和G（1）期细胞周期阻滞所必需的。E2F4是许多细胞类型中最丰富的E2F蛋白，在静止细胞中，它定位于细胞核，在那里它与视网膜母细胞瘤相关蛋白p130结合。在进入细胞周期的过程中，蛋白质从细胞核消失并出现在细胞质中，这种变化发生的机制在过去一直不清楚。我们已经发现，E2F4是积极的出口从核和来普霉素B，核输出的特异性抑制剂，抑制这一进程。E2F4输出由两个疏水输出序列介导，其中任一个中的突变导致输出失败。E2F4的单个输出突变体，但不是两个输出信号失活的突变体，可以通过强制共表达核输出受体CRM1有效地从核中排除。类似地，CRM1过表达可以阻止由细胞周期蛋白激酶抑制剂p16（INK4a）诱导的细胞周期停滞，这是一种E2F4依赖性过程。总之，这些数据表明，核输出有助于调节E2F4功能，包括其与合适的口袋蛋白相关的调节退出G（1）的能力。
E2F is a family of transcription factors required for normal cell cycle control and for cell cycle arrest in G(1). E2F4 is the most abundant E2F protein in many cell types, In quiescent cells, it is localized to the nucleus, where it is bound to the retinoblastoma-related protein p130. During entry into the cell cycle, the protein disappears from the nucleus and appears in the cytoplasm, The mechanism by which this change occurs has, in the past, been unclear. We have found that E2F4 is actively exported from the nucleus and that leptomycin B, a specific inhibitor of nuclear export, inhibits this process. E2F4 export is mediated by two hydrophobic export sequences, mutations in either of which result in export failure. Individual export mutants of E2F4, but not a mutant with inactivation of both export signals, can be efficiently excluded from the nucleus by forced coexpression of the nuclear export receptor CRM1. Similarly, CRM1 overexpression can prevent cell cycle arrest induced by the cyclin kinase inhibitor p16(INK4a), an E2F4-dependent process. Taken together, these data suggest that nuclear export contributes to the regulation of E2F4 function, including its ability to regulate exit from G(1) in association with a suitable pocket protein.