Fission yeast Tor1 functions as part of TORC1 to control mitotic entry through the stress MAPK pathway following nutrient stress
Fission yeast Tor1 functions as part of TORC1 to control mitotic entry through the stress MAPK pathway following nutrient stress
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DOI：
10.1242/jcs.049387
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发表时间：
2009-06-01
影响因子：
4
通讯作者：
Petersen, Janni
中科院分区：
文献类型：
--
作者：
Hartmuth, Sonya;Petersen, Janni
TOR信号传导协调生长和分裂以控制细胞大小。粟酒裂殖酵母Tor1的抑制，响应于氮源质量的降低（营养胁迫），通过激活促分裂原活化蛋白激酶（MAPK）Sty1（也称为Spc1）促进有丝分裂的开始。在这里，我们表明，“营养饥饿”（氮或亮氨酸的完全撤出）通过改变Sty1信号传导阻断有丝分裂承诺，不同程度的Sty1激活决定这些差异有丝分裂承诺的决定。哺乳动物含有一个TOR激酶，而酵母含有两个。在每种情况下，它们都包含两种不同的复合物：TORC 1和TORC 2。我们发现，营养应激诱导的控制有丝分裂的开始，通过Tor1，通过TORC 1信号的变化进行调节。在基本培养基中，Tor1与TORC1组分Mip1（raptor）相互作用，并且Tor1（+）的过表达产生TORC1突变体的生长缺陷。缺乏TORC 2特异性组分Sin1和Ste20（rictor）的菌株仍然在响应营养胁迫时提前有丝分裂开始。相比之下，Mip1和下游效应Gad8（S6K激酶同源物），如Tor1，是营养胁迫推进有丝分裂开始所必需的。我们的结论是S. pombe Tor1和Tor2都可以在TORC 1中起作用。然而，它是抑制Tor1作为TORC 1的一部分，促进营养胁迫后的有丝分裂。
TOR signalling coordinates growth and division to control cell size. Inhibition of Schizosaccharomyces pombe Tor1, in response to a reduction in the quality of the nitrogen source (nutrient stress), promotes mitotic onset through activation of the mitogen-activated protein kinase (MAPK) Sty1 (also known as Spc1). Here we show that 'nutrient starvation' (complete withdrawal of nitrogen or leucine) blocks mitotic commitment by altering Sty1 signalling and that different degrees of Sty1 activation determine these differences in mitotic commitment decisions. Mammals contain one TOR kinase, whereas yeasts contain two. In each case, they comprise two distinct complexes: TORC1 and TORC2. We find that nutrient-stress-induced control of mitotic onset, through Tor1, is regulated through changes in TORC1 signalling. In minimal medium, Tor1 interacts with the TORC1 component Mip1 (raptor), and overexpression of tor1(+) generates growth defects reminiscent of TORC1 mutants. Strains lacking the TORC2-specific components Sin1 and Ste20 (rictor) still advance mitotic onset in response to nutrient stress. By contrast, Mip1 and the downstream effector Gad8 (a S6K kinase homologue), like Tor1, are essential for nutrient stress to advance mitotic onset. We conclude that S. pombe Tor1 and Tor2 can both act in TORC1. However, it is the inhibition of Tor1 as part of TORC1 that promotes mitosis following nutrient stress.