Cytoplasmic-Nuclear Trafficking of G1/S Cell Cycle Molecules and Adult Human β-Cell Replication
| Autor: | Nathalie Fiaschi-Taesch, Jeffrey W. Kleinberger, Ronnie Troxell, Andrew F. Stewart, Harish Srinivas, Mansoor Tanwir, Donald K. Scott, Gabriella P. Casinelli, Fatimah G. Salim, Karen K. Takane, Amy E. Cox, Rachel C. Wills |
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| Rok vydání: | 2013 |
| Předmět: |
0303 health sciences
Cell division Cell growth Endocrinology Diabetes and Metabolism Cyclin A 030209 endocrinology & metabolism Cell cycle Biology 16. Peace & justice Cell biology 03 medical and health sciences Cell nucleus 0302 clinical medicine medicine.anatomical_structure Cytoplasm Internal Medicine medicine biology.protein Nuclear protein Cell Cycle Protein 030304 developmental biology |
| Zdroj: | Diabetes. 62:2460-2470 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Harnessing control of human β-cell proliferation has proven frustratingly difficult. Most G1/S control molecules, generally presumed to be nuclear proteins in the human β-cell, are in fact constrained to the cytoplasm. Here, we asked whether G1/S molecules might traffic into and out of the cytoplasmic compartment in association with activation of cell cycle progression. Cdk6 and cyclin D3 were used to drive human β-cell proliferation and promptly translocated into the nucleus in association with proliferation. In contrast, the cell cycle inhibitors p15, p18, and p19 did not alter their location, remaining cytoplasmic. Conversely, p16, p21, and p27 increased their nuclear frequency. In contrast once again, p57 decreased its nuclear frequency. Whereas proliferating β-cells contained nuclear cyclin D3 and cdk6, proliferation generally did not occur in β-cells that contained nuclear cell cycle inhibitors, except p21. Dynamic cytoplasmic-nuclear trafficking of cdk6 was confirmed using green fluorescent protein–tagged cdk6 and live cell imaging. Thus, we provide novel working models describing the control of cell cycle progression in the human β-cell. In addition to known obstacles to β-cell proliferation, cytoplasmic-to-nuclear trafficking of G1/S molecules may represent an obstacle as well as a therapeutic opportunity for human β-cell expansion. |
| Databáze: | OpenAIRE |
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