Cardiomyocyte Cyclin-dependent kinase 9 directly binds to and phosphorylates NF-κB p65 subunit to drive cardiac inflammation and remodeling - PubMed
4 hours ago
- #CDK9
- #NF-κB
- #cardiac remodeling
- CDK9 promotes inflammation and cardiac remodeling in cardiomyocytes.
- CDK9 phosphorylation at Thr-186 is found in hypertrophic heart tissues.
- CDK9 loss of function (T186A mutation) reduces Ang II-induced heart remodeling and NF-κB inflammation.
- CDK9 overactivation (T186E mutation) induces cardiac remodeling and inflammation.
- CDK9's role in cardiac remodeling is cell cycle-independent.
- CDK9 directly binds to NF-κB P65, leading to nuclear translocation and P65 phosphorylation.
- This process requires CDK9 Thr-186 phosphorylation and Cyclin T1, but is independent of IKKβ and CDK9-RNAPII pathways.
- Pharmacological inhibition of CDK9 phosphorylation reduces Ang II-induced cardiac inflammation and dysfunction in mice.
- CDK9 is identified as a potential therapeutic target for heart failure.