A unique binding mode of Nek2A to the APC/C allows its ubiquitination during prometaphase.

ABSTRACT: The anaphase-promoting complex (APC/C) is the key E3 ubiquitin ligase which directs mitotic progression and exit by catalysing the sequential ubiquitination of specific substrates. The activity of the APC/C in mitosis is restrained by the spindle assembly checkpoint (SAC), which coordinates chromosome segregation with the assembly of the mitotic spindle. The SAC effector is the mitotic checkpoint complex (MCC), which binds and inhibits the APC/C. It is incompletely understood how the APC/C switches substrate specificity in a cell cycle-specific manner. For instance, it is unclear how in prometaphase, when APC/C activity towards cyclin B and securin is repressed by the MCC, the kinase Nek2A is ubiquitinated. Here we combine biochemical and structural analysis with functional studies in cell

SUBMITTER: Dr. Claudio Alfieri 

PROVIDER: S-SCDT-EMBOR-2019-49831V1 | biostudies-other |

REPOSITORIES: biostudies-other