AMBRA1 and cancer: Three independent studies unveiled a novel ubiquitylation degradation mechanism of cyclin D. As a substrate receptor of the CULLIN 4/DDB1 complex, AMBRA1 directly binds and ubiquitinates cyclin D to promote its proteasomal degradation (34–36), while checkpoint kinase 1 (CHK1) is a key kinase in the replication stress response, and its inhibition aggravates DNA damage and leads to cell death in AMBRA1-null cancer cells (35).