Metabolic Stress-Induced Phosphorylation of KAP1 Ser473 Blocks Mitochondrial Fusion in Breast Cancer Cells.

ABSTRACT: Mitochondrial dynamics during nutrient starvation of cancer cells likely exert profound effects on their capability for metastatic progression. Here, we report that KAP1 (TRIM28), a transcriptional coadaptor protein implicated in metastatic progression in breast cancer, is a pivotal regulator of mitochondrial fusion in glucose-starved cancer cells. Diverse metabolic stresses induced Ser473 phosphorylation of KAP1 (pS473-KAP1) in a ROS- and p38-dependent manner. Results from live-cell imaging and molecular studies revealed that during the first 6 to 8 hours of glucose starvation, mitochondria initially underwent extensive fusion, but then subsequently fragmented in a pS473-KAP1-dependent manner. Mechanistic investigations using phosphorylation-defective mutants revealed that KAP1 Ser473 pho

SUBMITTER: Cheng CT 

PROVIDER: S-EPMC5316485 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature