![]() Canonical RB function in cell-cycle control is tightly regulated by cyclin-dependent kinase (CDK) and cyclin phosphorylation as well as upstream CDK inhibitor (CDKI) proteins. ![]() The retinoblastoma (RB) tumor suppressor protein serves as a transcriptional corepressor that is frequently altered in cancer and has been linked to both prevention of tumor development and progression. On balance, these findings reveal novel pathways through which RB loss promotes cancer progression and highlight potentially new nodes of intervention for treating RB-deficient cancers. These E2F1-dependent events resulted in protection from reactive oxygen species in response to therapeutic intervention. Biochemical and functional assessment using both in vitro and in vivo models identified an unexpected, prominent role for E2F1 in regulation of redox metabolism after RB loss, driving an increase in the synthesis of the antioxidant glutathione, specific to advanced disease. ![]() Here, isogenic modeling of RB loss identified disease stage–specific rewiring of E2F1 function, providing the first-in-field mapping of the E2F1 cistrome and transcriptome after RB loss across disease progression. Loss of the retinoblastoma (RB) tumor suppressor protein is a critical step in reprogramming biological networks that drive cancer progression, although mechanistic insight has been largely limited to the impact of RB loss on cell-cycle regulation. ![]()
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