當(dāng)增生細(xì)胞因“依賴于周期蛋白的激酶”(Cdk1)的受控活性而達(dá)到一定大小時(shí),,它們會(huì)分裂,但Cdk1調(diào)控因子與監(jiān)測(cè)細(xì)胞大小的機(jī)制之間的聯(lián)系一直不是很清楚,。
本期Nature上兩篇論文,,描述了一種裂殖酵母激酶Pom1(已知是細(xì)胞極性的一個(gè)決定因子)何以能夠在細(xì)胞內(nèi)形成一個(gè)度量桿狀細(xì)胞長(zhǎng)度的極性梯度、以及何以能夠通過(guò)對(duì)Cdk1抑制因子Wee1的負(fù)調(diào)控來(lái)誘導(dǎo)細(xì)胞分裂,。(生物谷Bioon.com)
生物谷推薦原始出處:
Nature 459, 852-856 (11 June 2009) | doi:10.1038/nature08054
Polar gradients of the DYRK-family kinase Pom1 couple cell length with the cell cycle
Sophie G. Martin1 & Martine Berthelot-Grosjean1
1 Center for Integrative Genomics, Faculty of Biology and Medicine, University of Lausanne, Génopode Building, 1015 Lausanne, Switzerland
Cells normally grow to a certain size before they enter mitosis and divide. Entry into mitosis depends on the activity of Cdk1, which is inhibited by the Wee1 kinase and activated by the Cdc25 phosphatase1. However, how cells sense their size for mitotic commitment remains unknown. Here we show that an intracellular gradient of the dual-specificity tyrosine-phosphorylation regulated kinase (DYRK) Pom1, which emanates from the ends of rod-shaped Schizosaccharomyces pombe cells, serves to measure cell length and control mitotic entry. Pom1 provides positional information both for polarized growth and to inhibit cell division at cell ends2, 3, 4, 5. We discovered that Pom1 is also a dose-dependent G2–M inhibitor. Genetic analyses indicate that Pom1 negatively regulates Cdr1 and Cdr2, two previously described Wee1 inhibitors of the SAD kinase family6, 7, 8, 9, 10. This inhibition may be direct, because in vivo and in vitro evidence suggest that Pom1 phosphorylates Cdr2. Whereas Cdr1 and Cdr2 localize to a medial cortical region, Pom1 forms concentration gradients from cell tips that overlap with Cdr1 and Cdr2 in short cells, but not in long cells. Disturbing these Pom1 gradients leads to Cdr2 phosphorylation and imposes a G2 delay. In short cells, Pom1 prevents precocious M-phase entry, suggesting that the higher medial Pom1 levels inhibit Cdr2 and promote a G2 delay. Thus, gradients of Pom1 from cell ends provide a measure of cell length to regulate M-phase entry.