High-throughput phenotypic screening followed by unbiased target identification reveals a new molecular glue HQ461 that induces CDK12-DDB1 interaction to promote degradation of Cyclin K via the ubiquitin proteasome system.
A multi-transcriptional CDKs inhibitor suppresses MYC and induces regression of ovarian tumors, indicating that targeting CDK7, 12, 13 with THZ1 may be an effective approach for treating MYC-dependent malignancies.
Quantitative phosphoproteomics defines the substrates for Cyclin A/Cdk1 kinase during early mitosis and follow up studies validate that one identified substrate, MYPT1, influences the stability of k-MT attachments by regulating Plk1.
Quantitative live-cell microscopy and molecular perturbations in Drosophila and human cells reveal a crosstalk between molecular 'rulers' (Aurora B) and 'clocks' (Cdk1) that coordinates mitotic exit in space and time.
Loss-of-function screening identified transglutaminase 2 (TGM2) as a putative tumor suppressor in the TP53 pathway and revealed that TGM2-mediated autophagy and CDKN1A-mediated cell cycle arrest are two critical barriers that prevent oncogenic transformation.
Ablation of the Cdkn1c cell cycle inhibitor leads to defective muscle stem cell dynamics and myogenic potential, while progressive cytoplasmic to nuclear cellular localization of the Cdkn1c protein regulates growth arrest.