Double identity of SCAPER: a substrate and regulator of cyclin A/Cdk2.
Cyclin A is a key regulator of DNA replication and mitosis, and cyclin A/Cdk2 activity is critical for progression of cells from G(1)/S to M phase of the cell cycle. There is abundant evidence that cyclin A is predominantly localized to, and functions in, the nucleus, and a number of nuclear cyclin A/Cdk2 substrates have been identified. Evidence supporting the presence of cyclin A and its associated activity in the cytoplasm have also been reported, but the biological significance of this cyclin/Cdk pool during cell cycle progression remains controversial. Recently, we identified and characterized a new cyclin A/Cdk2 substrate named SCAPER which is localized to the endoplasmic reticulum. By sequestering cyclin A/Cdk2, SCAPER is capable of directing the activity of this kinase complex away from the nucleus and regulating cyclin A/Cdk2 equilibrium in distinct subcellular compartments. This work paves new avenues for understanding the role of cytoplasmic cyclin A/Cdk2 and its potential contribution to cancer and tumor formation.
Tsang
William Y
WY
New York University School of Medicine, Department of Pathology, New York, New York 10016, USA.
Dynlacht
Brian David
BD
D002352:Carrier Proteins / Q000378:metabolism*; D019925:Cyclin A / Q000378:metabolism*; D051357:Cyclin-Dependent Kinase 2 / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D008938:Mitosis / Q000502:physiology*; D008954:Models, Biological
D002352:Carrier Proteins; D019925:Cyclin A; C523211:SCAPER protein, human; C495894:CDK2 protein, human; D051357:Cyclin-Dependent Kinase 2