uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
The 1p36 Tumor Suppressor KIF 1B beta Is Required for Calcineurin Activation, Controlling Mitochondrial Fission and Apoptosis
Ludwig Inst Canc Res Ltd, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Microbiol & Tumor & Cell Biol, S-17177 Stockholm, Sweden..
Ludwig Inst Canc Res Ltd, S-17177 Stockholm, Sweden.;Karolinska Inst, Dept Cell & Mol Biol, S-17177 Stockholm, Sweden..
Ludwig Inst Canc Res Ltd, S-17177 Stockholm, Sweden..
Karolinska Inst, Dept Med Biochem & Biophys, S-17177 Stockholm, Sweden..
Show others and affiliations
2016 (English)In: Developmental Cell, ISSN 1534-5807, E-ISSN 1878-1551, Vol. 36, no 2, 164-178 p.Article in journal (Refereed) PublishedText
Abstract [en]

KIF1B beta is a candidate 1p36 tumor suppressor that regulates apoptosis in the developing sympathetic nervous system. We found that KIF1B beta activates the Ca2+-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 Ca2+ signals and its deregulation is implicated in cancer, cardiac, neurodegenerative, and immune disease. We show that KIF1B beta affects mitochondria! dynamics through CN-dependent dephosphorylation of Dynamin-related protein 1 (DRP1), causing mitochondria! fission and apoptosis. Furthermore, KIF1B beta actuates recognition of all known CN substrates, implying a general mechanism for KIF1B beta in Ca2+ signaling and how Ca2+-dependent signaling is executed by CN. Pathogenic KIF1B beta mutations previously identified in neuroblastomas and pheochromocytomas all fail to activate CN or stimulate DRP1 dephosphorylation. Importantly, KIF1B beta and DRP1 are silenced in 1p36 hemizygous-deleted neuroblastomas, indicating that deregulation of calcineurin and mitochondria! dynamics contributes to high-risk and poor-prognosis neuroblastoma.

Place, publisher, year, edition, pages
2016. Vol. 36, no 2, 164-178 p.
National Category
Cancer and Oncology
URN: urn:nbn:se:uu:diva-279628DOI: 10.1016/j.devcel.2015.12.029ISI: 000369353400007PubMedID: 26812016OAI: oai:DiVA.org:uu-279628DiVA: diva2:910014
Swedish Childhood Cancer FoundationSwedish Research CouncilSwedish Cancer SocietySwedish Research Council
Available from: 2016-03-08 Created: 2016-03-02 Last updated: 2016-03-08Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Ludwig Institute for Cancer Research
In the same journal
Developmental Cell
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 17 hits
ReferencesLink to record
Permanent link

Direct link