Abstract
The dual specificity phosphatase and oncogene Cdc25B has been implicated in the G2/M cell cycle checkpoint, but the mode by which it is regulated remains poorly understood. Regional subcellular redistribution of proteins represents a unique potential regulatory mechanism. Thus, we examined in live cells the subcellular localization characteristics of Cdc25B2 and Cdc25B3 fused to green fluorescent protein. Cdc25B2 partitioned primarily in the cytoplasm during G1 and progressively migrated to the nucleus as cells transited from S to G2/M phase. In contrast, Cdc25B3 maintained a homogeneously staining diffuse phenotype irrespective of cell cycle phase. Treatment of the Cdc25B2-green fluorescent protein stable transfectants with vanadate inhibited the cell cycle dependency of intracellular distribution, while okadaic acid had little effect except in G1, suggesting regulation by at least one phosphorylation-dependent pathway. The DNA topoisomerase II poison and DNA damaging agent, etoposide, inhibited nuclear localization of Cdc25B2 in S phase, possibly by invoking a sequestration cascade. Thus, differences in the spatial distribution of Cdc25B subtypes exist within cells and the 41 amino acid insert in the N-terminus of the Cdc25B3 splice variant encodes an important inhibitory determinant for such regulation. The subcellular redistribution of Cdc25B2 could be functionally important for G2/M checkpoint regulation.
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References
Aitken A. . 1996 Trend Cell Biol. 6: 341–347.
Baldin V, Cans C, Knibiehler H and Ducommun B. . 1997a J. Biol. Chem. 272: 32731–32734.
Baldin V, Cans C, Superti-Furga G and Ducommun B. . 1997b Oncogene 14: 2485–2495.
Conklin DS, Galaktionov K and Beach D. . 1995 Proc. Natl. Acad. Sci. USA 92: 7892–7896.
Gabrielli BG, De Souza CPC, Tonks ID, Clark JM, Hayward NK and Ellem KAO. . 1996 J. Cell Sci. 109: 1081–1093.
Gabrielli BG, Clark JM, McCormack AK and Ellem KAO. . 1997a J. Biol. Chem. 272: 28607–28614.
Gabrielli BG, Clark JM, McCormack AK and Ellem KAO. . 1997b Oncogene 15: 749–758.
Galaktionov K and Beach D. . 1991 Cell 67: 1181–1194.
Galaktionov K, Lee AK, Eckstein J, Draetta G, Meckler J, Loda M and Beach D. . 1995 Science 269: 1575–1577.
Hoffmann I, Clarke PR, Marcote MJ, Karsenti E and Draetta G. . 1993 EMBO J. 12: 53.
Jinno S, Suto K, Nagata A, Igarashi M, Kanaoka Y, Nojima H and Okayama H. . 1994 EMBO J. 13: 1549–1556.
Kruk PA, Orren DK and Bohr VA. . 1997 Biochem. Biophys. Res. Comm. 233: 717–722.
Lammer C, Wagerer S, Saffrich R, Mertens D, Ansorge W and Hoffmann I. . 1998 J. Cell Science 111: 2445–2453.
Millar JBA, Blevitt J, Gerace L, Sadhu K, Featherstone C and Russell P. . 1991 Proc. Natl. Acad. Sci. USA 88: 10500–10504.
Morgan DO. . 1995 Nature 374: 131–134.
Muslin AJ, Tanner JW, Allen PM and Shaw AS. . 1996 Cell 84: 889–897.
Pastan I. . 1979 Meth. Enzymol. LVIII: 233–248.
Peng C-Y, Graves PR, Thoma RS, Wu Z, Shaw AS and Piwnica-Worms H. . 1997 Science 277: 1501–1505.
Sanchez Y, Wong C, Thoma RS, Richman R, Wu Z, Piwnica-Worms H and Elledge SJ. . 1997 Science 277: 1497–1501.
Sebastian B, Kakizuka A and Hunter T. . 1993 Proc. Natl. Acad. Sci. USA 90: 3521–3524.
Strausfeld U, Fernandez A, Capony J-P, Girard F, Lautredou N, Derancourt J, Labbe J-C and Lamb NJC. . 1994 J. Biol. Chem. 269: 5989–6000.
Woo ES and Lazo JS. . 1997 Cancer Res. 57: 4236–4241.
Xu X and Burke SP. . 1996 J. Biol. Chem. 271: 5118–5124.
Yaffe MB, Rittinger K, Volinia S, Caron PR, Aitken A, Leffers H, Gamblin SJ, Smerdon SJ and Cantley LC. . 1997 Cell 91: 961–971.
Zeng Y, Forbes KC, Wu Z, Moreno S, Piwnica-Worms H and Enoch T. . 1998 Nature 395: 507–510.
Acknowledgements
We thank Simon Watkins, Ciprian Almonte, Angela Wang and the members of the Lazo Laboratory for their assistance and thoughtful advice.
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Supported by NIH grants CA61299 and CA78039 (JSL), US Army grants BCRP-96 and PC970414 (JSL), The Fiske Drug Discovery Fund, and American Heart Association, Pennsylvania Affiliate (ESW). This work is dedicated to Emily E Dorrance. May we all fight cancer with her spirit.
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Woo, E., Rice, R. & Lazo, J. Cell cycle dependent subcellular distribution of Cdc25B subtypes. Oncogene 18, 2770–2776 (1999). https://doi.org/10.1038/sj.onc.1202614
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DOI: https://doi.org/10.1038/sj.onc.1202614