TORC1 of fission yeast is rapamycin-sensitive
TORC1 of fission yeast is rapamycin-sensitive
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裂殖酵母TORC1对雷帕霉素敏感
DOI：
10.1111/j.1365-2443.2012.01618.x
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发表时间：
2012
期刊：
影响因子：
2.1
通讯作者：
Maeda T
中科院分区：
文献类型：
--
作者：
Takahara T;Maeda T
雷帕霉素(TOR)蛋白激酶的靶标在调节细胞生长以响应营养供应方面起着核心作用。TOR形成两个不同的多蛋白复合体，称为TOR复合体1(TORC1)和TORC2。通常，只有TORC1的活性被免疫抑制剂雷帕霉素抑制。虽然雷帕霉素通过抑制TORC1而强烈地抑制萌发酵母的细胞生长，但裂殖酵母的生长似乎对雷帕霉素具有抗药性。在这里，我们证明了雷帕霉素在体外以类似于其他生物的TORC1的方式抑制PombeTORC1的激酶活性。我们进一步证明，雷帕霉素对TORC1的不完全抑制是产生明显的雷帕霉素耐药的基础。在咖啡因存在的情况下，可能会降低TORC1的活性，野生型Pombecells对雷帕霉素的生长是敏感的，这种方式依赖于TORC1。此外，用雷帕霉素加咖啡因处理Pombecells会诱导饥饿特异性基因表达和自噬，类似于TORC1活性降低的细胞。这些结果表明，雷帕霉素确实抑制了TORC1 Ins.Pombe，但这种抑制不足以导致生长缺陷。这些发现确立了雷帕霉素对TORC1抑制的普遍作用。
The target of rapamycin (TOR) protein kinase plays central roles in the regulation of cell growth in response to nutritional availability. TOR forms two distinct multiprotein complexes termed TOR complex 1 (TORC1) and TORC2. Typically, only the activity of TORC1 is inhibited by the immunosuppressant rapamycin. Although rapamycin strongly inhibits cell growth of the budding yeastSaccharomyces cerevisiaethrough inhibition of TORC1, growth of the fission yeastSchizosaccharomyces pombeappears to be resistant to rapamycin. Here, we demonstrate that rapamycin inhibits the kinase activity ofS. pombeTORC1in vitroin a similar manner to TORC1 of other organisms. We furthermore show that incomplete inhibition of TORC1 by rapamycin underlies the apparent rapamycin resistance ofS. pombe. In the presence of caffeine, which potentially lowers TORC1 activity, the growth of wild‐typeS. pombecells is sensitive to rapamycin in a TORC1‐dependent manner. Moreover, treatment ofS. pombecells with rapamycin plus caffeine induces starvation‐specific gene expression and autophagy, similarly to cells with reduced TORC1 activity. These results indicate that rapamycin does inhibit TORC1 inS. pombe, but the inhibition is not sufficient to cause a growth defect. These findings establish a universal action of rapamycin on TORC1 inhibition.