Lu and Pfeffer uncover a protein that helps remove Cyclin E after it has outlasted its usefulness.
Cyclin E pushes cells from G1 into S phase. But if the protein lingers in cells, they can’t progress normally through the rest of the cell cycle. During S phase, the SCF pathway directs phosphorylated Cyclin E to the proteasome for destruction. A second, little-known pathway removes unphosphorylated Cyclin E. This pathway includes the protein Cullin3 (CUL3), which forms part of a ubiquitylating complex. CUL3 partners with proteins in the BTB family, which enable the complex to grab its targets. Lu and Pfeffer tested whether the Golgi-localized BTB protein RhoBTB3 promotes the elimination of Cyclin E.
Cells missing RhoBTB3 arrested in S phase with elevated Cyclin E levels. The Golgi apparatus in these cells also broke up, suggesting that RhoBTB3 helps structure the organelle. RhoBTB3 joined the same ubiquitin-adding complex as CUL3, and it latched onto Cyclin E molecules to spur their ubiquitylation.
The researchers determined that RhoBTB3 functioned properly only if it was located on the Golgi apparatus, yet much of the cell’s Cyclin E resides in the nucleus. However, some Cyclin E gathers near the centrosome, which is adjacent to the Golgi apparatus. RhoBTB3 might ensure that the cell disposes of this stockpile of Cyclin E, preventing the centrosome from duplicating more than once.
Text by Mitch Leslie