A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT Journal Article
| Authors: | Ganiatsas, S.; Dow, R.; Thompson, A.; Schulman, B.; Germain, D. |
| Article Title: | A splice variant of Skp2 is retained in the cytoplasm and fails to direct cyclin D1 ubiquitination in the uterine cancer cell line SK-UT |
| Abstract: | Cyclin D1 is an important regulator of the transition from G1 into S phase of the cell cycle. The level to which cyclin D1 accumulates is tightly regulated. One mechanism contributing to the control of cyclin D1 levels is the regulation of its ubiquitination. SK-UT-1B cells are deficient in the degradation of D-type cyclins. We show here that p27, a substrate of the SCFSkp2 ubiquitin ligase complex, is coordinately stabilized in SK-UT-1B cells. Further, we show that expression of Skp2 in SK-UT-1B cells rescues the cyclin D1 and p27 degradation defect observed in this cell line. These results therefore indicate that the SCFSkp2 ubiquitin ligase complex affects the ubiquitination of cyclin D1. In addition, we show that SK-UT-1B cells express a novel splice variant of Skp2 that localizes to the cytoplasm and that cyclin D1 ubiquitination takes place in the nucleus. We propose that the translocation of Skp2 into the nucleus is required for the ubiquitination of cyclin D1 and that the absence of the SCFSkp2 complex in the nucleus of SK-UT-1B cells is the mechanism underlying the ubiquitination defect observed in this cell line. Finally, our data indicates that differential splicing of F-box proteins may represent an additional level of regulation of the F-box mediated ubiquitination pathway. |
| Keywords: | controlled study; protein expression; unclassified drug; human cell; cell cycle proteins; cell cycle; ubiquitin protein ligase; protein degradation; cell protein; intracellular transport; tumor cells, cultured; protein processing; regulatory mechanism; ubiquitination; amino acid sequence; molecular sequence data; cancer cell; protein p27; protein transport; alternative splicing; cytoplasm; base sequence; cell nucleus; cyclin d1; uterus cancer; uterine neoplasms; ubiquitin-protein ligases; protein structure, secondary; isoenzymes; s phase kinase associated protein 2; s-phase kinase-associated proteins; cullin proteins; dna, complementary; ubiquitins; ligases; p27; scf; humans; human; female; priority journal; article |
| Journal Title: | Oncogene |
| Volume: | 20 |
| Issue: | 28 |
| ISSN: | 0950-9232 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2001-06-21 |
| Start Page: | 3641 |
| End Page: | 3650 |
| Language: | English |
| DOI: | 10.1038/sj.onc.1204501 |
| PUBMED: | 11439327 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Export Date: 21 May 2015 -- Source: Scopus |
