Cytoplasmic Localization of Human Cdc25C During Interphase Requires an Intact 14-3-3 Binding Site

Overview

Journal Mol Cell Biol

Specialty Cell Biology

Date 1999 May 18

PMID 10330186

Citations 82

Authors

S N Dalal

C M Schweitzer

J Gan

J A DeCaprio

Affiliations

Soon will be listed here.

Abstract

cdc25C induces mitosis by activating the cdc2-cyclin B complex. The intracellular localization of cyclin B1 is regulated in a cell cycle-specific manner, and its entry into the nucleus may be required for the initiation of mitosis. To determine the cellular localization of cdc25C, monoclonal antibodies specific for cdc25C were developed and used to demonstrate that in human cells, cdc25C is retained in the cytoplasm during interphase. A deletion analysis identified a 58-amino-acid region (amino acids 201 to 258) in cdc25C that was required for the cytoplasmic localization of cdc25C. This region contained a specific binding site for 14-3-3 proteins, and mutations in cdc25C that disrupted 14-3-3 binding also disrupted the cytoplasmic localization of cdc25C during interphase. cdc25C proteins that do not contain a binding site for 14-3-3 proteins showed a pancellular localization and an increased ability to induce premature chromosome condensation. The cytoplasmic localization of cdc25C was not altered by gamma irradiation or treatment with the nuclear export inhibitor leptomycin B. These results suggest that 14-3-3 proteins may negatively regulate cdc25C function by sequestering cdc25C in the cytoplasm.

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References

Zalvide J, Stubdal H, DeCaprio J . The J domain of simian virus 40 large T antigen is required to functionally inactivate RB family proteins. Mol Cell Biol. 1998; 18(3):1408-15. PMC: 108854. DOI: 10.1128/MCB.18.3.1408. View

Lee M, Ogg S, Xu M, Parker L, Donoghue D, Maller J . cdc25+ encodes a protein phosphatase that dephosphorylates p34cdc2. Mol Biol Cell. 1992; 3(1):73-84. PMC: 275503. DOI: 10.1091/mbc.3.1.73. View

Toyoshima F, Moriguchi T, Wada A, Fukuda M, Nishida E . Nuclear export of cyclin B1 and its possible role in the DNA damage-induced G2 checkpoint. EMBO J. 1998; 17(10):2728-35. PMC: 1170613. DOI: 10.1093/emboj/17.10.2728. View

Jin P, Hardy S, MORGAN D . Nuclear localization of cyclin B1 controls mitotic entry after DNA damage. J Cell Biol. 1998; 141(4):875-85. PMC: 2132764. DOI: 10.1083/jcb.141.4.875. View

Hermeking H, Lengauer C, Polyak K, He T, Zhang L, Thiagalingam S . 14-3-3sigma is a p53-regulated inhibitor of G2/M progression. Mol Cell. 1998; 1(1):3-11. DOI: 10.1016/s1097-2765(00)80002-7. View

Hagting A, Karlsson C, Clute P, JACKMAN M, Pines J . MPF localization is controlled by nuclear export. EMBO J. 1998; 17(14):4127-38. PMC: 1170745. DOI: 10.1093/emboj/17.14.4127. View

Yang J, Bardes E, Moore J, Brennan J, Powers M, Kornbluth S . Control of cyclin B1 localization through regulated binding of the nuclear export factor CRM1. Genes Dev. 1998; 12(14):2131-43. PMC: 317017. DOI: 10.1101/gad.12.14.2131. View

Kumagai A, Guo Z, Emami K, Wang S, Dunphy W . The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts. J Cell Biol. 1998; 142(6):1559-69. PMC: 2141764. DOI: 10.1083/jcb.142.6.1559. View

Zeng Y, Forbes K, Wu Z, Moreno S, Piwnica-Worms H, Enoch T . Replication checkpoint requires phosphorylation of the phosphatase Cdc25 by Cds1 or Chk1. Nature. 1998; 395(6701):507-10. DOI: 10.1038/26766. View

10.

Matsuoka S, Huang M, Elledge S . Linkage of ATM to cell cycle regulation by the Chk2 protein kinase. Science. 1998; 282(5395):1893-7. DOI: 10.1126/science.282.5395.1893. View

11.

Lopez-Girona A, Furnari B, Mondesert O, Russell P . Nuclear localization of Cdc25 is regulated by DNA damage and a 14-3-3 protein. Nature. 1999; 397(6715):172-5. DOI: 10.1038/16488. View

12.

Lee M, Enoch T, Piwnica-Worms H . mik1+ encodes a tyrosine kinase that phosphorylates p34cdc2 on tyrosine 15. J Biol Chem. 1994; 269(48):30530-7. View

13.

Gautier J, Solomon M, Booher R, Bazan J, Kirschner M . cdc25 is a specific tyrosine phosphatase that directly activates p34cdc2. Cell. 1991; 67(1):197-211. DOI: 10.1016/0092-8674(91)90583-k. View

14.

Davis F, Tsao T, Fowler S, Rao P . Monoclonal antibodies to mitotic cells. Proc Natl Acad Sci U S A. 1983; 80(10):2926-30. PMC: 393946. DOI: 10.1073/pnas.80.10.2926. View

15.

Munro S, Pelham H . Use of peptide tagging to detect proteins expressed from cloned genes: deletion mapping functional domains of Drosophila hsp 70. EMBO J. 1984; 3(13):3087-93. PMC: 557822. DOI: 10.1002/j.1460-2075.1984.tb02263.x. View

16.

Evan G, LEWIS G, Ramsay G, Bishop J . Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product. Mol Cell Biol. 1985; 5(12):3610-6. PMC: 369192. DOI: 10.1128/mcb.5.12.3610-3616.1985. View

17.

Lee W, Shew J, Hong F, SERY T, Donoso L, Young L . The retinoblastoma susceptibility gene encodes a nuclear phosphoprotein associated with DNA binding activity. Nature. 1987; 329(6140):642-5. DOI: 10.1038/329642a0. View

18.

Field J, Nikawa J, Broek D, Macdonald B, Rodgers L, Wilson I . Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol. 1988; 8(5):2159-65. PMC: 363397. DOI: 10.1128/mcb.8.5.2159-2165.1988. View

19.

Schreiber E, Matthias P, Muller M, Schaffner W . Rapid detection of octamer binding proteins with 'mini-extracts', prepared from a small number of cells. Nucleic Acids Res. 1989; 17(15):6419. PMC: 318318. DOI: 10.1093/nar/17.15.6419. View

20.

Kumagai A, Dunphy W . The cdc25 protein controls tyrosine dephosphorylation of the cdc2 protein in a cell-free system. Cell. 1991; 64(5):903-14. DOI: 10.1016/0092-8674(91)90315-p. View