This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Juan, G. Articles by Cordon-Cardo, C. Search for Related Content PubMed PubMed Citation Articles by Juan, G. Articles by Cordon-Cardo, C.

Intranuclear Compartmentalization of Cyclin E during the Cell Cycle: Disruption of the Nucleoplasm-Nucleolar Shuttling of Cyclin E in Bladder Cancer¹

Department of Pathology, Memorial Sloan-Kettering Cancer Center, New York, New York 10021

Cyclin E/cyclin-dependent kinase 2 complexes are essential during the cell cycle for entrance into S phase. Cyclin E expression starts in mid-G₁, reaches a maximum at S-phase entrance, and undergoes proteolysis mediated by the ubiquitin pathway as the cell progresses through S phase. Laser scanning cytometry, a microscope-based cytofluorometer combining the advantages of both flow and image analysis, allowed the determination of subcellular localization of cyclin E, p27, and retinoblastoma protein during cell cycle progression in normal human fibroblasts and nine bladder cancer cell lines. We observed that in normal fibroblasts and most tumor cell lines, cyclin E localizes in the nucleoplasm during mid-G₁ and is translocated to the nucleolus during G₁-S-phase transition, and its levels are undetectable in G₂-M phase. Neither levels nor subcellular localization of p27 and retinoblastoma protein was cell cycle dependent in normal or tumor cells. However, four of nine bladder cancer cell lines continued to express cyclin E in all phases of the cycle, and image analysis revealed that it was localized to nucleoli. These observations suggest that the nucleolus mediates a cyclin E "shuttling" between the nucleus and the cytoplasm that is probably involved in its regulation and that this mechanism could be disrupted in bladder cancer.

This article has been cited by other articles:

				L. B. Maggi Jr., M. Kuchenruether, D. Y. A. Dadey, R. M. Schwope, S. Grisendi, R. R. Townsend, P. P. Pandolfi, and J. D. Weber Nucleophosmin Serves as a Rate-Limiting Nuclear Export Chaperone for the Mammalian Ribosome Mol. Cell. Biol., December 1, 2008; 28(23): 7050 - 7065. [Abstract] [Full Text] [PDF]

				W. C. Zimmerman and R. L. Erikson Polo-like kinase 3 is required for entry into S phase PNAS, February 6, 2007; 104(6): 1847 - 1852. [Abstract] [Full Text] [PDF]

				Y. Yu, L. B. Maggi Jr., S. N. Brady, A. J. Apicelli, M.-S. Dai, H. Lu, and J. D. Weber Nucleophosmin Is Essential for Ribosomal Protein L5 Nuclear Export Mol. Cell. Biol., May 15, 2006; 26(10): 3798 - 3809. [Abstract] [Full Text] [PDF]

				A. M. Egloff, L. A. Vella, and O. J. Finn Cyclin B1 and Other Cyclins as Tumor Antigens in Immunosurveillance and Immunotherapy of Cancer Cancer Res., January 1, 2006; 66(1): 6 - 9. [Abstract] [Full Text] [PDF]

				C. Geisen and T. Moroy The Oncogenic Activity of Cyclin E Is Not Confined to Cdk2 Activation Alone but Relies on Several Other, Distinct Functions of the Protein J. Biol. Chem., October 11, 2002; 277(42): 39909 - 39918. [Abstract] [Full Text] [PDF]

				A. K. Sood, M. S. Fletcher, L. M. Gruman, J. E. Coffin, S. Jabbari, Z. Khalkhali-Ellis, N. Arbour, E. A. Seftor, and M. J. C. Hendrix The Paradoxical Expression of Maspin in Ovarian Carcinoma Clin. Cancer Res., September 1, 2002; 8(9): 2924 - 2932. [Abstract] [Full Text] [PDF]

				J. Mora, N.-K. V. Cheung, G. Juan, P. Illei, I. Cheung, M. Akram, S. Chi, M. Ladanyi, C. Cordon-Cardo, and W. L. Gerald Neuroblastic and Schwannian Stromal Cells of Neuroblastoma Are Derived from a Tumoral Progenitor Cell Cancer Res., September 1, 2001; 61(18): 6892 - 6898. [Abstract] [Full Text] [PDF]