Cyclin A/Cdk2 plays an important role during S and G2/M phases of the eukaryotic cell cycle, but the mechanisms by which it regulates cell cycle events are not fully understood. We have biochemically purified and identified SCAPER, a novel protein that specifically interacts with cyclin A/Cdk2 in vivo. Its expression is cell cycle independent, and it associates with cyclin A/Cdk2 at multiple phases of the cell cycle. SCAPER localizes primarily to the endoplasmic reticulum. Ectopic expression of SCAPER sequesters cyclin A from the nucleus and results specifically in an accumulation of cells in M phase of the cell cycle. RNAi-mediated depletion of SCAPER decreases the cytoplasmic pool of cyclin A and delays the G1/S phase transition upon cell cycle re-entry from quiescence. We propose that SCAPER represents a novel cyclin A/Cdk2 regulatory protein that transiently maintains this kinase in the cytoplasm. SCAPER could play a role in distinguishing S phase– from M phase–specific functions of cyclin A/Cdk2.
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13 August 2007
Article|
August 13 2007
SCAPER, a novel cyclin A–interacting protein that regulates cell cycle progression
William Y. Tsang,
William Y. Tsang
1Department of Pathology, New York University School of Medicine, New York, NY 10016
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Leyu Wang,
Leyu Wang
2Global Research and Development, Cambridge USA Laboratories, Pfizer Inc., Cambridge, MA 02139
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Zhihong Chen,
Zhihong Chen
3Esai Research Institute, Andover, MA 01810
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Irma Sánchez,
Irma Sánchez
1Department of Pathology, New York University School of Medicine, New York, NY 10016
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Brian David Dynlacht
Brian David Dynlacht
1Department of Pathology, New York University School of Medicine, New York, NY 10016
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William Y. Tsang
1Department of Pathology, New York University School of Medicine, New York, NY 10016
Leyu Wang
2Global Research and Development, Cambridge USA Laboratories, Pfizer Inc., Cambridge, MA 02139
Zhihong Chen
3Esai Research Institute, Andover, MA 01810
Irma Sánchez
1Department of Pathology, New York University School of Medicine, New York, NY 10016
Brian David Dynlacht
1Department of Pathology, New York University School of Medicine, New York, NY 10016
Correspondence to Brian D. Dynlacht: [email protected]
W.Y. Tsang and L. Wang contributed equally to this paper.
Abbreviations used in this paper: FACS, fluorescence-activated cell sorting; HU, hydroxyurea; RXL, cyclin-binding motif; SCAPER, S phase cyclin A–associated protein residing in the endoplasmic reticulum.
Received:
January 30 2007
Accepted:
July 13 2007
Online ISSN: 1540-8140
Print ISSN: 0021-9525
The Rockefeller University Press
2007
J Cell Biol (2007) 178 (4): 621–633.
Article history
Received:
January 30 2007
Accepted:
July 13 2007
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Citation
William Y. Tsang, Leyu Wang, Zhihong Chen, Irma Sánchez, Brian David Dynlacht; SCAPER, a novel cyclin A–interacting protein that regulates cell cycle progression . J Cell Biol 13 August 2007; 178 (4): 621–633. doi: https://doi.org/10.1083/jcb.200701166
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