The RUN domain of rubicon is important for hVps34 binding, lipid kinase inhibition, and autophagy suppression.
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.
Division of Biochemistry and Molecular Biology, Department of Molecular and Cell Biology, University of California, Berkeley, California 94720, USA.
Qiming
Q
Sun
Jing
J
Zhang
Weiliang
W
Fan
Kwun Ngok
KN
Wong
Xiaojun
X
Ding
She
S
Chen
Qing
Q
Zhong
D001343:Autophagy; D000071183:Autophagy-Related Proteins; D058546:Class III Phosphatidylinositol 3-Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism*; D057809:HEK293 Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D000071183:Autophagy-Related Proteins; D047908:Intracellular Signaling Peptides and Proteins; C552537:RUBCN protein, human; D025521:Tumor Suppressor Proteins; C408122:UVRAG protein, human; D058546:Class III Phosphatidylinositol 3-Kinases