| First Author | Li S | Year | 2016 |
| Journal | Dev Cell | Volume | 36 |
| Issue | 2 | Pages | 164-78 |
| PubMed ID | 26812016 | Mgi Jnum | J:249969 |
| Mgi Id | MGI:6098774 | Doi | 10.1016/j.devcel.2015.12.029 |
| Citation | Li S, et al. (2016) The 1p36 Tumor Suppressor KIF 1Bbeta Is Required for Calcineurin Activation, Controlling Mitochondrial Fission and Apoptosis. Dev Cell 36(2):164-78 |
| abstractText | KIF1Bbeta is a candidate 1p36 tumor suppressor that regulates apoptosis in the developing sympathetic nervous system. We found that KIF1Bbeta activates the Ca(2+)-dependent phosphatase calcineurin (CN) by stabilizing the CN-calmodulin complex, relieving enzymatic autoinhibition and enabling CN substrate recognition. CN is the key mediator of cellular responses to Ca(2+) signals and its deregulation is implicated in cancer, cardiac, neurodegenerative, and immune disease. We show that KIF1Bbeta affects mitochondrial dynamics through CN-dependent dephosphorylation of Dynamin-related protein 1 (DRP1), causing mitochondrial fission and apoptosis. Furthermore, KIF1Bbeta actuates recognition of all known CN substrates, implying a general mechanism for KIF1Bbeta in Ca(2+) signaling and how Ca(2+)-dependent signaling is executed by CN. Pathogenic KIF1Bbeta mutations previously identified in neuroblastomas and pheochromocytomas all fail to activate CN or stimulate DRP1 dephosphorylation. Importantly, KIF1Bbeta and DRP1 are silenced in 1p36 hemizygous-deleted neuroblastomas, indicating that deregulation of calcineurin and mitochondrial dynamics contributes to high-risk and poor-prognosis neuroblastoma. |
