THE 2ND-CODON RULE AND AUTOPHOSPHORYLATION GOVERN THE STABILITY AND ACTIVITY OF MOS DURING THE MEIOTIC CELL-CYCLE IN XENOPUS-OOCYTES
THE 2ND-CODON RULE AND AUTOPHOSPHORYLATION GOVERN THE STABILITY AND ACTIVITY OF MOS DURING THE MEIOTIC CELL-CYCLE IN XENOPUS-OOCYTES
复制标题
DOI：
10.1002/j.1460-2075.1992.tb05308.x
复制
发表时间：
1992-07-01
期刊：
影响因子：
11.4
通讯作者：
SAGATA, N
中科院分区：
文献类型：
--
作者：
NISHIZAWA, M;OKAZAKI, K;SAGATA, N
c-mos 原癌基因产物 Mos 在非洲爪蟾卵母细胞减数分裂成熟过程中的早期（生发囊泡破裂）和晚期（中期 11 停滞）中发挥作用。在早期阶段，Mos仅部分磷酸化且代谢不稳定，而在后期阶段则完全磷酸化且高度稳定。使用卵母细胞中表达的许多 Mos 突变体，我们在此表明，Mos 在早期步骤中的不稳定性主要由其倒数第二个 N 末端残基决定，或者由此处称为“第二密码子规则”的规则决定。我们证明不稳定的 Mos 可以通过泛素依赖性途径降解。另一方面，在最后的步骤中，Mos 通过 Ser3 处的自磷酸化而稳定，这可能起到防止 Mos 的 N 末端被泛素蛋白连接酶识别的作用。此外，我们发现 Ser3 磷酸化对于 Mos 在完全成熟的卵母细胞中发挥其全部细胞生长抑制因子 (CSF) 活性至关重要。因此，一些N端氨基酸是减数分裂细胞周期中Mos代谢稳定性和生理活性的主要决定因素。
The c-mos proto-oncogene product, Mos, functions in both early (germinal vesicle breakdown) and late (metaphase 11 arrest) steps during meiotic maturation in Xenopus oocytes. In the early step, Mos is only partially phosphorylated and metabolically unstable, while in the late step it is fully phosphorylated and highly stable. Using a number of Mos mutants expressed in oocytes, we show here that the instability of Mos in the early step is determined primarily by its penultimate N-terminal residue, or by a rule referred to here as the 'second-codon rule'. We demonstrate that unstable Mos is degraded by the ubiquitin-dependent pathway. In the late step, on the other hand, Mos is stabilized by autophosphorylation at Ser3, which probably acts to prevent the N-terminus of Mos from being recognized by a ubiquitin-protein ligase. Moreover, we show that Ser3 phosphorylation is essential for Mos to exert its full cytostatic factor (CSF) activity in fully mature oocytes. Thus, a few N-terminal amino acids are primary determinants of both the metabolic stability and physiological activity of Mos during the meiotic cell cycle.