Publication:
Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma

dc.contributor.authorAli, Fahad R
dc.date.accessioned2021-08-03T10:06:27Z
dc.date.available2021-08-03T10:06:27Z
dc.date.issued2020
dc.description.abstractAbstract: Pediatric cancers often resemble trapped developmental intermediate states that fail to engage the normal differentiation program, typified by high-risk neuroblastoma arising from the developing sympathetic nervous system. Neuroblastoma cells resemble arrested neuroblasts trapped by a stable but aberrant epigenetic program controlled by sustained expression of a core transcriptional circuit of developmental regulators in conjunction with elevated MYCN or MYC (MYC). The transcription factor ASCL1 is a key master regulator in neuroblastoma and has oncogenic and tumor suppressive activities in several other tumor types. Using functional mutational approaches, we find that preventing CDK-dependent phosphorylation of ASCL1 in neuroblastoma cells drives coordinated suppression of the MYC-driven core circuit supporting neuroblast identity and proliferation, while simultaneously activating an enduring gene program driving mitotic exit and neuronal differentiation.en_US
dc.identifier.issn204-2020.68
dc.identifier.urihttps://repository.mbru.ac.ae/handle/1/379
dc.language.isoenen_US
dc.subjectPediatric canceren_US
dc.subjectDephosphorylationen_US
dc.subjectASCL1en_US
dc.subjectNeuroblastoma.en_US
dc.titleDephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastomaen_US
dc.typeArticleen_US
dspace.entity.typePublicationen_US

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