Here we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7 as inhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1 or the more selective YKL-1-116.

Aug 19, 2021 · Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, with p53 and GSDME protein level elevation.

Feb 14, 2024 · Once p53 was activated by 5-fluorouracil or nutlin-3, transcription depended on CDK7. These works suggest that p53-activating agents may synergize with CDK7 inhibitors to induce cell death.

Our study aimed to explore a novel mechanism of CDK7 inhibition for suppressing breast cancer cell survival. Here, we proved inhibiting CDK7 repressed breast cancer cell proliferation and colony formation and increased the apoptotic cell rate, …

Sep 5, 2022 · Here, we aimed to explore whether elevated p53 protein expression increases WT p53 breast cancer cell sensitivity to THZ1 or extensive transcriptional process abolishment, but not to CDK7 inhibition.

The tumor suppressor protein p53 acts as a transcriptional activator that can mediate cellular responses to DNA damage by inducing apoptosis and cell cycle arrest. p53 is a nuclear phosphoprotein, and phosphorylation has been proposed to be a means by which the activity of p53 is regulated.

Oct 10, 2017 · Here, we show that p53 activation by 5-fluorouracil or nutlin-3 synergizes with a reversible Cdk7 as inhibitor to induce cell death. Synthetic lethality was recapitulated with covalent inhibitors of wild-type Cdk7, THZ1, or the more selective YKL-1-116.

Mar 14, 2025 · Additionally, CDK7 influences transcription factors through phosphorylation. It enhances estrogen receptor alpha (ERα) activity in hormone-driven cancers and modulates p53’s ability to activate DNA damage response genes. These roles position CDK7 as a key regulator of gene expression programs.

Our findings reveal that CDK7 might serve as a novel putative pro-oncogenic gene underlying HNSCC tumorigenesis and therapeutic targeting of CDK7 might be a promising strategy for p53-mutated HNSCC.

Cdk7, associated with the transcription initiation factor TFIIH, is both an effector CDK that phosphorylates Pol II and other targets within the transcriptional machinery, and a CDK-activating kinase (CAK) for at least one other essential CDK involved in transcription.