Caspase-mediated cleavage of importin-alpha increases its affinity for MCM and downregulates DNA synthesis by interrupting the binding of MCM to chromatin.
Importin-alpha is essential for classical nucleocytoplasmic transport of nuclear proteins. Here, we report that importin-alpha is cleaved by caspases during apoptosis, generating importin-alpha lacking an IBB domain. This truncated importin-alpha binds tightly to the MCM replication licensing factor and, thus, prevents its binding to chromatin and downregulates DNA synthesis. Together, our data reveal for the first time that a dying cell effectively salvages limited supplies of cellular energy to ensure an orderly process of its own demise by simultaneously downregulating nucleocytoplasmic protein transport and DNA synthesis. Strikingly, cells can achieve this multi-task process by simply cleaving-off a key nuclear import protein.
Kim
Byung Ju
BJ
Department of Biochemistry, Microbiology and Immunology, Faculty of Medicine, the University of Ottawa, Ottawa, Ontario, Canada K1H 5M8.
Lee
Hoyun
H