Publication: Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma
dc.contributor.author | Ali, Fahad R | |
dc.date.accessioned | 2021-08-03T10:06:27Z | |
dc.date.available | 2021-08-03T10:06:27Z | |
dc.date.issued | 2020 | |
dc.description.abstract | Abstract: 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.issn | 204-2020.68 | |
dc.identifier.uri | https://repository.mbru.ac.ae/handle/1/379 | |
dc.language.iso | en | en_US |
dc.subject | Pediatric cancer | en_US |
dc.subject | Dephosphorylation | en_US |
dc.subject | ASCL1 | en_US |
dc.subject | Neuroblastoma. | en_US |
dc.title | Dephosphorylation of the Proneural Transcription Factor ASCL1 Re-Engages a Latent Post-Mitotic Differentiation Program in Neuroblastoma | en_US |
dc.type | Article | en_US |
dspace.entity.type | Publication | en_US |