LST8 通过雷帕霉素靶蛋白复合物 2（TORC2）调控细胞生长。
LST8 regulates cell growth via target-of-rapamycin complex 2 (TORC2).
机构信息
Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
出版信息
Mol Cell Biol. 2012 Jun;32(12):2203-13. doi: 10.1128/MCB.06474-11. Epub 2012 Apr 9.
Abstract
The evolutionarily conserved serine/threonine protein kinase target-of-rapamycin (TOR) controls cell growth as a core component of TOR complexes 1 (TORC1) and 2 (TORC2). Although TORC1 is the more central growth regulator, TORC2 has also been shown to affect cell growth. Here, we demonstrate that Drosophila LST8, the only conserved TOR-binding protein present in both TORC1 and TORC2, functions exclusively in TORC2 and is not required for TORC1 activity. In mutants lacking LST8, expression of TOR and RAPTOR, together with their upstream activator Rheb, was sufficient to provide TORC1 activity and stimulate cell and organ growth. Furthermore, using an lst8 knockout mutation, we show that TORC2 regulates cell growth cell autonomously. Surprisingly, however, TORC2 does not regulate cell growth via its best-characterized target, AKT. Our findings support the possible application of TORC2-specific drugs in cancer therapy.
摘要
进化保守的丝氨酸/苏氨酸蛋白激酶雷帕霉素靶蛋白（TOR）作为 TOR 复合物 1（TORC1）和 2（TORC2）的核心组成部分，控制着细胞生长。尽管 TORC1 是更核心的生长调节剂，但 TORC2 也被证明会影响细胞生长。在这里，我们证明果蝇 LST8 是唯一存在于 TORC1 和 TORC2 中的保守 TOR 结合蛋白，它专门在 TORC2 中发挥作用，而不需要 TORC1 活性。在缺乏 LST8 的突变体中，表达 TOR 和 RAPTOR 及其上游激活因子 Rheb 足以提供 TORC1 活性并刺激细胞和器官生长。此外，我们使用 lst8 敲除突变证明 TORC2 能够自主调节细胞生长。然而，令人惊讶的是，TORC2 并不通过其最具特征性的靶标 AKT 来调节细胞生长。我们的发现支持在癌症治疗中应用 TORC2 特异性药物的可能性。
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