TFEB CONTROLS VASCULAR DEVELOPMENT BY REGULATING THE PROLIFERATION OF ENDOTHELIAL CELLS

ABSTRACT: Transcription factor TFEB is thought to control cellular functions - including in the vascular bed - primarily via regulation of lysosomal biogenesis and autophagic flux. Here, we report that TFEB also orchestrates a non-canonical program that controls the cell-cycle/VEGFR2 pathway in the developing vasculature. In endothelial cells, TFEB depletion halts proliferation at the G1-S transition by inhibiting the CDK4/Rb pathway. TFEB-deficient cells attempt to compensate for this limitation by increasing VEGFR2 levels at the plasma membrane via microRNA-mediated mechanisms and controlled membrane trafficking. TFEB stimulates expression of the miR-15a/16-1 cluster, which limits VEGFR2 transcript stability and negatively modulates expression of MYO1C, a regulator of VEGFR2 trafficking to the cel

SUBMITTER: Dr. Gabriella Doronzo 

PROVIDER: S-SCDT-EMBOJ-2017-98250 | biostudies-other |

REPOSITORIES: biostudies-other