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Publication : Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors.

First Author  Wajapeyee N Year  2013
Journal  Genes Dev Volume  27
Issue  20 Pages  2221-6
PubMed ID  24105743 Mgi Jnum  J:202816
Mgi Id  MGI:5522578 Doi  10.1101/gad.227413.113
Citation  Wajapeyee N, et al. (2013) Oncogenic RAS directs silencing of tumor suppressor genes through ordered recruitment of transcriptional repressors. Genes Dev 27(20):2221-6
abstractText  We previously identified 28 cofactors through which a RAS oncoprotein directs transcriptional silencing of Fas and other tumor suppressor genes (TSGs). Here we performed RNAi-based epistasis experiments and found that RAS-directed silencing occurs through a highly ordered pathway that is initiated by binding of ZFP354B, a sequence-specific DNA-binding protein, and culminates in recruitment of the DNA methyltransferase DNMT1. RNAi and pharmacological inhibition experiments reveal that silencing requires continuous function of RAS and its cofactors and can be rapidly reversed, which may have therapeutic implications for reactivation of silenced TSGs in RAS-positive cancers.
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