PTEN counteracts FBXL2 to promote IP3R3- and Ca²⁺-mediated apoptosis limiting tumour growth.

ABSTRACT: In response to environmental cues that promote IP3 (inositol 1,4,5-trisphosphate) generation, IP3 receptors (IP3Rs) located on the endoplasmic reticulum allow the 'quasisynaptical' feeding of calcium to the mitochondria to promote oxidative phosphorylation. However, persistent Ca²⁺ release results in mitochondrial Ca²⁺ overload and consequent apoptosis. Among the three mammalian IP3Rs, IP3R3 appears to be the major player in Ca²⁺-dependent apoptosis. Here we show that the F-box protein FBXL2 (the receptor subunit of one of 69 human SCF (SKP1, CUL1, F-box protein) ubiquitin ligase complexes) binds IP3R3 and targets it for ubiquitin-, p97- and proteasome-mediated degradation to limit Ca²⁺ influx into mitochondria. FBXL2-knockdown cells and FBXL2-in

SUBMITTER: Kuchay S 

PROVIDER: S-EPMC5627969 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature