Figure 6.

Cyclin C-Cdk8/19/3 inhibit the Notch pathway by phosphorylating the Notch intracellular fragment (NICD) and promoting its degradation in leukemic T cells. In canonical Notch signaling, a contiguous cell exposes a Notch ligand which is recognized by a Notch receptor paralog on a receiving cell. Subsequently, a two-step proteolytic cleavage produces NICD which stimulates with a transcriptionally paused RNA Pol II complex resulting in the downstream expression of genes involved in stem cell differentiation and self-renewal.