Ufd2, a novel autoantigen in scleroderma, regulates sister chromatid separation Journal Article
| Authors: | Spinette, S.; Lengauer, C.; Mahoney, J. A.; Jallepalli, P. V.; Wang, Z.; Casciola-Rosen, L.; Rosen, A. |
| Article Title: | Ufd2, a novel autoantigen in scleroderma, regulates sister chromatid separation |
| Abstract: | The characterization of molecules recognized by patients with autoimmune diseases has provided significant insights into important biological pathways. In these studies, we define Ufd2 (a novel E4 polyubiquitylating enzyme) as a new autoantigen in scleroderma, and show that it regulates chromosome condensation and separation during mitosis in human cells. Ufd2 is regulated by phosphorylation in mitosis. Inhibition of Ufd2 expression results in mitotic arrest at the metaphase-anaphase transition, where cells manifest abnormal chromosome morphology, missegregated chromosomes, irregular spindles, and premature separation of sister chromatids. This is accompanied by premature separase activation, and accumulation of securin in a novel modified form. We further demonstrate that Ufd2 directly and efficiently ubiquitylates securin in vitro and is required for securin polyubiquitylation in vivo. This is the first description of a physiologic substrate for Ufd2, establishing this E4 enzyme as an important regulator of chromosome condensation and separation during mitosis in human cells. Its targeting in scleroderma, together with many other components of the mitotic machinery, reinforces the concept that mitotic cells may be an important focus of the autoimmune response in this disease. ©2004 Landes Bioscience. |
| Keywords: | controlled study; protein expression; protein phosphorylation; unclassified drug; human cell; case-control studies; protein function; mitosis; chromosome structure; cell cycle proteins; in situ hybridization, fluorescence; sister chromatid; apoptosis; neoplasm proteins; protein; rna, small interfering; enzyme activation; hela cells; phosphorylation; gene expression regulation; ubiquitination; tumor suppressor proteins; epithelial cells; autoantigen; autoantigens; anaphase; autoantibodies; metaphase; chromosome segregation; nocodazole; chromatids; securin; separase; endopeptidases; k562 cells; phase transition; ubiquitylation; scleroderma; chromosome condensation; humans; human; article; ufd2; ubiquitin fusion degradation 2 protein; scleroderma, systemic |
| Journal Title: | Cell Cycle |
| Volume: | 3 |
| Issue: | 12 |
| ISSN: | 1538-4101 |
| Publisher: | Taylor & Francis Inc. |
| Date Published: | 2004-12-01 |
| Start Page: | 1638 |
| End Page: | 1644 |
| Language: | English |
| PROVIDER: | scopus |
| PUBMED: | 15611659 |
| DOI/URL: | |
| Notes: | Cell Cycle -- Cited By (since 1996):5 -- Export Date: 16 June 2014 -- Source: Scopus |
