The kinesin KIF1Bbeta acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor.

Abstract	VHL, NF-1, c-Ret, and Succinate Dehydrogenase Subunits B and D act on a developmental apoptotic pathway that is activated when nerve growth factor (NGF) becomes limiting for neuronal progenitor cells and requires the EglN3 prolyl hydroxylase as a downstream effector. Germline mutations of these genes cause familial pheochromocytoma and other neural crest-derived tumors. Using an unbiased shRNA screen we found that the kinesin KIF1Bbeta acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. KIF1Bbeta maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function KIF1Bbeta missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that KIF1Bbeta is a pathogenic target of these deletions.
Authors	Susanne Schlisio, Rajappa S Kenchappa, Liesbeth C W Vredeveld, Rani E George, Rodney Stewart, Heidi Greulich, Kristina Shahriari, Nguyen V Nguyen, Pascal Pigny, Patricia L Dahia, Scott L Pomeroy, John M Maris, A Thomas Look, Matthew Meyerson, Daniel S Peeper, Bruce D Carter, William G Kaelin Jr
Journal	Genes & development (Genes Dev) Vol. 22 Issue 7 Pg. 884-93 (Apr 01 2008) ISSN: 0890-9369 [Print] United States
PMID	18334619 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
Chemical References	DNA-Binding Proteins Immediate-Early Proteins Kif1b protein, mouse Nerve Tissue Proteins Tumor Suppressor Proteins Procollagen-Proline Dioxygenase Egln1 protein, mouse Hypoxia-Inducible Factor-Proline Dioxygenases Kinesins
Topics	Animals Animals, Newborn Apoptosis Cells, Cultured Child Chromosome Mapping Chromosomes, Mammalian (genetics) DNA-Binding Proteins (genetics, metabolism) HeLa Cells Humans Hypoxia-Inducible Factor-Proline Dioxygenases Immediate-Early Proteins (genetics, metabolism) Immunoblotting Kinesins (genetics, metabolism) Medulloblastoma (genetics, pathology) Mice Mice, Knockout Models, Biological Mutation, Missense Nerve Tissue Proteins (genetics, metabolism) Neuroblastoma (genetics, pathology) Neurons (cytology, metabolism) PC12 Cells Pheochromocytoma (genetics, pathology) Procollagen-Proline Dioxygenase RNA Interference Rats Tumor Suppressor Proteins (genetics, metabolism)

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