RNA helicase A is necessary for KIF1Bβ tumor suppression in neuroblastoma

ABSTRACT: During development neuronal progenitors compete for growth factors such as nerve growth factor NGF and require the prolyl hydroxylase EglN3 and the kinesin KIF1Bβ for developmental apoptosis. Inherited KIF1Bβ loss-of-function mutations in neuroblastomas and pheochromocytomas implicate KIF1Bβ as a 1p36.2 tumor suppressor, however the mechanism of tumor suppression is unknown. We found that KIF1Bβ interacts with the RNA helicase A (DHX9) resulting in DHX9 nuclear accumulation to regulate apoptosis. KIF1Bβ-dependent DHX9 nuclear localization leads to transcription of the apoptotic target XIAP-associated factor 1. DHX9 is induced when NGF is limiting and required for apoptosis in cells deprived of NGF. NB1 cells were transduced to incorporate shRNA against DHX9 or a scrambled control, and transfected with a KIF1Bβ expression vector or control, then transfected cells were isolated and lysed after 48h.

ORGANISM(S): Homo sapiens

SUBMITTER: Daniel Ramsköld 

PROVIDER: E-GEOD-44585 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress