Phosphorylation-independent regulation of Atf1-promoted meiotic recombination by stress-activated, p38 kinase Spc1 of fission yeast.
Phosphorylation-independent regulation of Atf1-promoted meiotic recombination by stress-activated, p38 kinase Spc1 of fission yeast.
复制标题
DOI：
10.1371/journal.pone.0005533
复制
发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Wahls WP
中科院分区：
文献类型：
--
作者：
Gao J;Davidson MK;Wahls WP
应激激活的蛋白激酶调节多种细胞对各种细胞内外条件的反应。裂解酵母中保守的、多功能的ATF/CREB蛋白atf1(Mts1，Gad7)与Cre样(M26)DNA结合。ATF1被保守的p38家族的蛋白激酶SPc1(Sty1，Phh1)磷酸化，是许多依赖Spc1的胁迫反应、有效的性别分化和激活依赖于Rec12(Spo11)的减数分裂重组热点(如ade6-M26)所必需的。我们试图定义SPc1在ade6-M26热点调控atf1功能的机制。SPc1激酶对热点活性是必需的，但对基础重组是不可缺少的。出乎意料的是，一个缺乏全部11个MAPK磷酸受体位点和可检测到的磷酸化(atf1-11m)的蛋白质完全能够进行热点重组。此外，通过异源DNA结合域将染色体中的atf1到ade6连接在一起，绕过了对spc1促进重组的要求。SPc1蛋白激酶在atf1与染色体结合的点或之前调节atf1促进的重组途径，该途径的调节不依赖于atf1的磷酸化状态。由于基础重组是不依赖于spc1的，所以在减数分裂重组中，spc1激酶的主要功能是将atf1启动的重组正确地定位在染色体上的热点。我们还对多功能应激激活蛋白atf1的共享(如DNA结合)和不同(如渗透压调节与重组)活性的调节机制提出了新的假设。
Stress-activated protein kinases regulate multiple cellular responses to a wide variety of intracellular and extracellular conditions. The conserved, multifunctional, ATF/CREB protein Atf1 (Mts1, Gad7) of fission yeast binds to CRE-like (M26) DNA sites. Atf1 is phosphorylated by the conserved, p38-family kinase Spc1 (Sty1, Phh1) and is required for many Spc1-dependent stress responses, efficient sexual differentiation, and activation of Rec12 (Spo11)-dependent meiotic recombination hotspots like ade6-M26. We sought to define mechanisms by which Spc1 regulates Atf1 function at the ade6-M26 hotspot. The Spc1 kinase was essential for hotspot activity, but dispensable for basal recombination. Unexpectedly, a protein lacking all eleven MAPK phospho-acceptor sites and detectable phosphorylation (Atf1-11M) was fully proficient for hotspot recombination. Furthermore, tethering of Atf1 to ade6 in the chromosome by a heterologous DNA binding domain bypassed the requirement for Spc1 in promoting recombination. The Spc1 protein kinase regulates the pathway of Atf1-promoted recombination at or before the point where Atf1 binds to chromosomes, and this pathway regulation is independent of the phosphorylation status of Atf1. Since basal recombination is Spc1-independent, the principal function of the Spc1 kinase in meiotic recombination is to correctly position Atf1-promoted recombination at hotspots along chromosomes. We also propose new hypotheses on regulatory mechanisms for shared (e.g., DNA binding) and distinct (e.g., osmoregulatory vs. recombinogenic) activities of multifunctional, stress-activated protein Atf1.
登录
查看更多内容
影响因子：
5.3
作者：
Degols, G;Russell, P
通讯作者：
Russell, P
DOI：
10.1073/pnas.94.14.7446
发表时间：
1997-07-08
影响因子：
11.1
作者：
Fox, ME;Virgin, JB;Smith, GR
通讯作者：
Smith, GR
影响因子：
4.8
作者：
Lawrence, Clare L.;Maekarwa, Hiromi;Jones, Nic
通讯作者：
Jones, Nic
影响因子：
16
作者：
Alepuz, PM;Jovanovic, A;Ammerer, G
通讯作者：
Ammerer, G
影响因子：
3.3
作者：
Chen, DR;Toone, WM;Bähler, J
通讯作者：
Bähler, J