May 3, 2019 · Alterations of the cyclin-dependent kinase (CDK)–RB–E2F axis occur in virtually all cancers and result in heightened oncogenic E2F activity and uncontrolled proliferation.

May 26, 2023 · Here, we show that E2F1 induction and RB depletion induce PVR and PD-L1 protein expression in TNBC cells. Overexpression of E2F1 and acute RB depletion via RNAi invariably induced PVR and PD-L1.

This suggests that the effects of CDK inhibitors are mediated, at least in part, by increasing deregulated E2F1 activity, supporting the proposed treatment strategy of enhancing deregulated E2F activity in cancer cells, specifically inducing apoptosis.

Determining the mechanism underlying this tumor suppressor function may expose novel strategies to block Rb-pathway cancers. p107/p130 are best known as E2f inhibitors, but here we implicate E2f-independent Cdk2 inhibition as the critical p107 tumor suppressor function in vivo.

Nov 6, 2018 · To elucidate more critical CCA molecular pathways involved in post-traumatic neuronal cell death, we investigated the neuroprotective effects and mechanisms of the potent CDK inhibitor CR8 in a...

Jan 30, 2023 · Cyclin dependent kinases (CDK) regulate the interaction of RB/E2F by phosphorylating RB. Previously, we have revealed that CDK2, RB and E2F inhibit ferroptosis. Ferroptosis is a non-apoptotic, iron-dependent form of cell …

Cyclin A/CDK2 binds directly to E2F-1 and inhibits the DNA-binding activity of E2F-1/DP-1 by phosphorylation. E2F-1, a member of the E2F transcription factor family, contributes to the regulation of the G1-to-S phase transition in higher eukaryotic cells.

In this study, we investigate how DNA damage elicited by exposure to the topoisomerase I inhibitor camptothecin (CPT) leads to cycle-related death of cultured cortical neurons and examine the function of E2F1 in this process.

Nov 6, 2018 · To elucidate more critical CCA molecular pathways involved in post-traumatic neuronal cell death, we investigated the neuroprotective effects and mechanisms of the potent CDK inhibitor CR8 in a DNA damage model of cell death in primary cortical neurons.

Oct 10, 2022 · Inhibition of CDK1/CDK2 prevented DNA damage induced by E2F loss, suggesting that E2F1/E2F2 safeguard genome integrity by restraining CDK1/CDK2 activity. Importantly, combined inhibition of E2F and ATR boosted replication stress and dramatically reduced tumorigenic capacity of PCa cells in xenografts.