The proteasome destroys damaged and unnecessary proteins in cells, but how it was regulated during cell growth and division was not known. Now Xing Guo, Jack Dixon, and colleagues at the University of California, San Diego, and University of California, Irvine found that the 26S proteasome was specifically phosphorylated during the cell cycle and that blocking this phosphorylation could halt cell cycle progression. They identified the kinase responsible for proteasome phosphorylation, dual-specificity tyrosine-regulated kinase 2 (DYRK2), and found that inhibiting phosphorylation or knock-down of the DYRK2 could inhibit tumor formation in mice. Published in Nature Cell Biology.