miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1

Warning The system is temporarily closed to updates for reporting purpose.

Korkmaz, Gözde and Le Sage, Carlos and Tekirdağ, Kumsal Ayşe and Agami, Reuven and Gözüaçık, Devrim (2012) miR-376b controls starvation and mTOR inhibition-related autophagy by targeting ATG4C and BECN1. Autophagy, 8 (2). pp. 165-176. ISSN 1554-8627

This is the latest version of this item.

[img]PDF - Registered users only - Requires a PDF viewer such as GSview, Xpdf or Adobe Acrobat Reader

Official URL: http://dx.doi.org/10.4161/auto.8.2.18351


Macroautophagy (autophagy) is the major intracellular degradation pathway for long-lived proteins and organelles. It helps the cell to survive a spectrum of stressful conditions including starvation, growth factor deprivation and misfolded protein accumulation. Moreover, abnormalities of autophagy play a role in major health problems including cancer and neurodegenerative diseases. Yet, mechanisms controlling autophagic activity are not fully understood. Here, we describe hsa-miR-376b (miR-376b) as a new microRNA (miRNA) regulating autophagy. We showed that miR-376b expression attenuated starvation- and rapamycin-induced autophagy in MCF-7 and Huh-7 cells. We discovered autophagy proteins ATG4C and BECN1 (Beclin 1) as cellular targets of miR-376b. Indeed, upon miRNA overexpression, both mRNA and protein levels of ATG4C and BECN1 were decreased. miR-376b target sequences were present in the 3' UTR of ATG4C and BECN1 mRNAs and introduction of mutations abolished their miR-376b responsiveness. Antagomir-mediated inactivation of the endogenous miR-376b led to an increase in ATG4C and BECN1 levels. Therefore, miR-376b controls autophagy by directly regulating intracellular levels of two key autophagy proteins, ATG4C and BECN1.

Item Type:Article
Additional Information:DG is the corresponding author
Uncontrolled Keywords:Macroautophagy, mammalian autophagy regulation, microRNA, hsa-miR-376b, Beclin1, Atg4C, drug research
Subjects:Q Science > Q Science (General)
R Medicine > R Medicine (General)
R Medicine > RB Pathology
Q Science > QL Zoology
Q Science > QP Physiology
ID Code:18952
Deposited By:Devrim Gözüaçık
Deposited On:06 Apr 2012 15:42
Last Modified:31 Jul 2019 09:22

Available Versions of this Item

Repository Staff Only: item control page