STAT3 localizes to the ER, acting as a gatekeeper for ER-mitochondrion Ca²⁺ fluxes and apoptotic responses.

ABSTRACT: STAT3 is an oncogenic transcription factor exerting its functions both as a canonical transcriptional activator and as a non-canonical regulator of energy metabolism and mitochondrial functions. While both activities are required for cell transformation downstream of different oncogenic stimuli, they rely on different post-translational activating events, namely phosphorylation on either Y705 (nuclear activities) or S727 (mitochondrial functions). Here, we report the discovery of the unexpected STAT3 localization to the endoplasmic reticulum (ER), from where it modulates ER-mitochondria Ca²⁺ release by interacting with the Ca²⁺ channel IP3R3 and facilitating its degradation. The release of Ca²⁺ is of paramount importance for life/death cell decisions, as ex

SUBMITTER: Avalle L 

PROVIDER: S-EPMC6214529 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature