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Published online August 13, 2007
doi:10.1083/jcb.200701166
The Journal of Cell Biology, Vol. 178, No. 4, 621-633
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Tsang et al.
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Article

 SCAPER, a novel cyclin A–interacting protein that regulates cell cycle progression

William Y. Tsang1, Leyu Wang2, Zhihong Chen3, Irma Sánchez1, and Brian David Dynlacht1

1 Department of Pathology, New York University School of Medicine, New York, NY 10016
2 Global Research and Development, Cambridge USA Laboratories, Pfizer Inc., Cambridge, MA 02139
3 Esai Research Institute, Andover, MA 01810

Correspondence to Brian D. Dynlacht: brian.dynlacht{at}med.nyu.edu

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.

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.


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