Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis
Drosophila Myt1 is a Cdk1 inhibitory kinase that regulates multiple aspects of cell cycle behavior during gametogenesis
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DOI：
10.1242/dev.01965
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发表时间：
2005-09-01
期刊：
影响因子：
4.6
通讯作者：
Campbell, SD
中科院分区：
文献类型：
--
作者：
Jin, ZG;Homola, EM;Campbell, SD
后生动物Wee1样激酶Wee1和Myt1通过抑制磷酸化调节有丝分裂调节因子Cdk1。这种调节机制，防止Cdk1触发过早的有丝分裂事件，也诱导DNA损伤反应过程中，并用于协调细胞增殖与关键的发育事件。尽管先前已经证明了Myt 1在减数分裂过程中对Cdk 1的调节作用，但对Myt 1在其他发育阶段的功能知之甚少。为了解决这个问题，我们已经进行了果蝇Myt 1的功能分析，揭示了这种保守的细胞周期调控在配子发生过程中的新的发展作用。值得注意的是，在myt1突变体睾丸和卵巢中观察到比对照组更多的增殖细胞。这可以部分归因于myt1突变体中生殖系相关体细胞的异位分裂，表明Myt1在调节细胞周期退出中起作用。此外，有丝分裂指数的测量表明，生殖干细胞增殖更迅速，在myt1突变的女性。此外，雄性myt1生殖细胞偶尔会进行额外的有丝分裂，导致减数分裂囊肿的细胞数量是正常的两倍。基于这些观察结果，我们提出，Myt1提供独特的Cdk1调节功能所需的细胞分化与细胞周期进程的有效耦合。
The metazoan Wee1-like kinases Wee1 and Myt1 regulate the essential mitotic regulator Cdk1 by inhibitory phosphorylation. This regulatory mechanism, which prevents Cdk1 from triggering premature mitotic events, is also induced during the DNA damage response and used to coordinate cell proliferation with crucial developmental events. Despite the previously demonstrated role for Myt1 regulation of Cdk1 during meiosis, relatively little is known of how Myt1 functions at other developmental stages. To address this issue, we have undertaken a functional analysis of Drosophila Myt1 that has revealed novel developmental roles for this conserved cell cycle regulator during gametogenesis. Notably, more proliferating cells were observed in myt1 mutant testes and ovaries than controls. This can partly be attributed to ectopic division of germline-associated somatic cells in myt1 mutants, suggesting that Myt1 serves a role in regulating exit from the cell cycle. Moreover, mitotic index measurements suggested that germline stem cells proliferate more rapidly, in myt1 mutant females. In addition, male myt1 germline cells occasionally undergo an extra mitotic division, resulting in meiotic cysts with twice the normal numbers of cells. Based on these observations, we propose that Myt1 serves unique Cdk1 regulatory functions required for efficient coupling of cell differentiation with cell cycle progression.