The kinesin KIF1Bβ acts downstream from EglN3 to induce apoptosis and is a potential 1p36 tumor suppressor
書誌事項
- 公開日
- 2008-03-11
- DOI
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- 10.1101/gad.1648608
- 公開者
- Cold Spring Harbor Laboratory
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説明
<jats:p><jats:italic>VHL</jats:italic>, <jats:italic>NF-1</jats:italic>, <jats:italic>c-Ret</jats:italic>, and <jats:italic>Succinate Dehydrogenase Subunits B</jats:italic> and <jats:italic>D</jats:italic> 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 KIF1Bβ acts downstream from EglN3 and is both necessary and sufficient for neuronal apoptosis when NGF becomes limiting. <jats:italic>KIF1Bβ</jats:italic> maps to chromosome 1p36.2, which is frequently deleted in neural crest-derived tumors including neuroblastomas. We identified inherited loss-of-function <jats:italic>KIF1Bβ</jats:italic> missense mutations in neuroblastomas and pheochromocytomas and an acquired loss-of-function mutation in a medulloblastoma, arguing that <jats:italic>KIF1Bβ</jats:italic> is a pathogenic target of these deletions.</jats:p>
収録刊行物
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- Genes & Development
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Genes & Development 22 (7), 884-893, 2008-03-11
Cold Spring Harbor Laboratory