SCAPER (red) keeps cyclin A (green) in the cytoplasm to promote S phase progression.

Cyclin A promotes the progression of both S phase and mitosis. A new cyclin A binding protein, identified by Tsang et al. (page 621), helps the S phase push but hinders mitotic progression. The new partner seems to favor S phase by holding cyclin A in the cytoplasm.

To determine how cyclin A pushes forward different stages of the cell cycle, Dynlacht's team looked for new binding partners. They fished out one especially strong candidate, which was associated with the ER, and named it SCAPER (S phase cyclin A–associated protein of the endoplasmic reticulum).

Overexpression of SCAPER delayed progression of cells through M phase, suggesting that the protein blocks this cyclin A activity. But SCAPER deletion prevented cells from entering S phase in a timely manner, conversely indicating that it normally helps cyclin A in this case.

This S phase delay, the authors propose, might be due to cyclin A's entering the nucleus too soon. Recent findings indicate that, although cyclin A is predominantly nuclear, it phosphorylates certain cytoplasmic proteins. Perhaps tethering cyclin A at the ER keeps it in the cytoplasm long enough for necessary S phase–promoting interactions.

The nuclear allotment of cyclin A might be more important for G2 and M phase progression. Too much SCAPER would thus block mitosis by preventing its nuclear entry. Under normal conditions, cyclin A levels would be sufficiently high by G2 that SCAPER can no longer restrain all of it.