Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
J Biol Chem. 2011 Jan 7;286(1):185-91. doi: 10.1074/jbc.M110.126425. Epub 2010 Nov 9.
The class III phosphatidylinositol 3-kinase (PI3KC3) plays a central role in autophagy. Rubicon, a RUN domain-containing protein, is newly identified as a PI3KC3 subunit through its association with Beclin 1. Rubicon serves as a negative regulator of PI3KC3 and autophagosome maturation. The molecular mechanism underlying the PI3KC3 and autophagy inhibition by Rubicon is largely unknown. Here, we demonstrate that Rubicon interacts with the PI3KC3 catalytic subunit hVps34 via its RUN domain. The RUN domain contributes to the efficient inhibition of PI3KC3 lipid kinase activity by Rubicon. Furthermore, a Rubicon RUN domain deletion mutant fails to complement the autophagy deficiency in Rubicon-depleted cells. Hence, these results reveal a critical role of the Rubicon RUN domain in PI3KC3 and autophagy regulation.
III 类磷酸肌醇 3-激酶（PI3KC3）在自噬中起着核心作用。Rubicon 是一种新发现的含有 RUN 结构域的蛋白，通过与 Beclin 1 结合而成为 PI3KC3 的一个亚基。Rubicon 作为 PI3KC3 的负调节剂和自噬体成熟的负调节剂。Rubicon 抑制 PI3KC3 和自噬的分子机制在很大程度上尚不清楚。在这里，我们证明 Rubicon 通过其 RUN 结构域与 PI3KC3 的催化亚基 hVps34 相互作用。RUN 结构域有助于 Rubicon 有效地抑制 PI3KC3 脂质激酶活性。此外，Rubicon RUN 结构域缺失突变体不能弥补 Rubicon 耗尽细胞中的自噬缺陷。因此，这些结果揭示了 Rubicon RUN 结构域在 PI3KC3 和自噬调节中的关键作用。
