Chemistry

Cell

Gene

Mitosis

Cell biology

Biology

Cyclin A

Cyclin-dependent kinase

Ubiquitin ligase

Cell division control protein 4

Cell cycle

Ubiquitin

Biochemistry

Nature

Mammalian cells integrate mitogen and stress signalling before the end of G1 phase to determine whether or not they enter the cell cycle1–4. Before cells can replicate their DNA in S phase, they have to activate cyclin-dependent kinases (CDKs), induce an E2F transcription program and inactivate the anaphase-promoting complex (APC/CCDH1, also known as the cyclosome), which is an E3 ubiquitin ligase that contains the co-activator CDH1 (also known as FZR, encoded by FZR1). It was recently shown that stress can return cells to quiescence after CDK2 activation and E2F induction but not after inactivation of APC/CCDH1, which suggests that APC/CCDH1 inactivation is the point of no return for cell-cycle entry                  3                . Rapid inactivation of APC/CCDH1 requires early mitotic inhibitor 1 (EMI1)3,5, but the molecular mechanism that controls this cell-cycle commitment step is unknown. Here we show using human cell models that cell-cycle commitment is mediated by an EMI1–APC/CCDH1 dual-negative fe...

EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle