The existence of two distinct Wee1 isoforms in Xenopus:: implications for the developmental regulation of the cell cycle

The existence of two distinct Wee1 isoforms in Xenopus:: implications for the developmental regulation of the cell cycle
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DOI:
10.1093/emboj/21.10.2472
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发表时间:
2002-05-15
期刊:
影响因子:
11.4
通讯作者:
Sagata, N
Sagata, N
中科院分区:
生物学1区
文献类型:
--
作者:
Okamoto, K;Nakajo, N;Sagata, N

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在真核细胞中,Wee 1蛋白激酶磷酸化并抑制Cdc 2,从而产生细胞周期的间期。在非洲爪蟾中,传统的Wee 1同源物(称为Xe-Wee 1A,或简称Wee 1A)在母体中表达,并在具有快速细胞周期的前原肠胚胚胎中发挥作用。在这里,我们已经分离出第二个,合子异构体的爪蟾Wee 1,称为Xe-Wee 1B(或Wee 1B的简称),这是在postgastrula胚胎和各种成人组织中表达。当异位表达在未成熟的卵母细胞,Wee 1B抑制Cdc 2活性和卵母细胞成熟(或进入M期)比Wee 1A更强烈,由于其短的C-末端调控结构域。此外,与Wee 1A不同,异位Wee 1B在减数分裂11期间非常不稳定,并且由于其N-末端调节结构域中存在PEST样序列而不能在成熟卵母细胞中积累。最后,当在受精卵中表达时,异位Wee 1B而不是Wee 1A确实影响早期胚胎中的细胞分裂并损害细胞活力,主要是由于其非常强的激酶活性。这些结果强烈表明,Wee 1A和Wee 1B的差异表达是至关重要的发育调控的细胞周期在非洲爪蟾。
In eukaryotic cells, the Wee1 protein kinase phosphorylates and inhibits Cdc2, thereby creating an interphase of the cell cycle. In Xenopus, the conventional Wee1 homolog (termed Xe-Wee1A, or Wee1A for short) is maternally expressed and functions in pregastrula embryos with rapid cell cycles. Here, we have isolated a second, zygotic isoform of Xenopus Wee1, termed Xe-Wee1B (or Wee1B for short), that is expressed in postgastrula embryos and various adult tissues. When ectopically expressed in immature oocytes, Wee1B inhibits Cdc2 activity and oocyte maturation (or entry into M phase) much more strongly than Wee1A, due to its short C-terminal regulatory domain. Moreover, ectopic Wee1B, unlike Wee1A, is very labile during meiosis 11 and cannot accumulate in mature oocytes due to the presence of PEST-like sequences in its N-terminal regulatory domain. Finally, when expressed in fertilized eggs, ectopic Wee1B but not Wee1A does affect cell division and impair cell viability in early embryos, due primarily to its very strong kinase activity. These results suggest strongly that the differential expression of Wee1A and Wee1B is crucial for the developmental regulation of the cell cycle in Xenopus.