Before and after the spindle assembly checkpoint - An APC/C point of view
ABSTRACT On May 17-21, 2006 the Cold Spring Harbor Laboratory meeting on the cell cycle reunited over 350 researchers to discuss new findings in the cell cycle field. A common thread that connected numerous presentations was the regulation of the anaphase promoting complex/cyclosome (APC/C). This was also the main theme of the lecture given by the keynote speaker, Marc Kirschner (Harvard), who talked about "The unexpected importance of UbcH10 in both the G(1)/S transition and the initiation of anaphase", and it is also the main focus in this summary.
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ABSTRACT: UbcH10 participates in proper metaphase to anaphase transition, and abrogation of UbcH10 results in the premature separation of sister chromatids. To assess the potential role of UbcH10 in colon cancer progression, we analyzed the clinicopathological relevance of UbcH10 in colon cancer. We firstly screened the expression profile of UbcH10 in various types of cancer tissues as well as cell lines. Thereafter, using the colon cancer cells line, we manipulated the expression of UbcH10 and evaluated the cell cycle profile and cellular proliferations. Furthermore, the clinicopathological significance of UbcH10 was immunohistologically evaluated in patients with colon cancer. Statistical analysis was performed using the student's t-test and Chi-square test. Using the colon cancer cells, depletion of UbcH10 resulted in suppression of cellular growth whereas overexpression of UbcH10 promoted the cellular growth and oncogenic cellular growth. Mitotic population was markedly alternated by the manipulation of UbcH10 expression. Immunohistochemical analysis indicated that UbcH10 was significantly higher in colon cancer tissue compared with normal colon epithelia. Furthermore, the clinicopathological evaluation revealed that UbcH10 was associated with high-grade histological tumors. The results show the clinicopathological significance of UbcH10 in the progression of colon cancer. Thus UbcH10 may act as a novel biomarker in patients with colon cancer.BMC Cancer 02/2009; 9:87. DOI:10.1186/1471-2407-9-87 · 3.32 Impact Factor
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ABSTRACT: UbcH10 is a component of the Ubiquitin Conjugation Enzymes (Ubc; E2) involved in the ubiquitination cascade controlling the cell cycle progression, whereby ubiquitin, activated by E1, is transferred through E2 to the target protein with the involvement of E3 enzymes. In this work we propose the first three dimensional model of the tetrameric complex formed by the human UbA1 (E1), two ubiquitin molecules and UbcH10 (E2), leading to the transthiolation reaction. The 3D model was built up by using an experimentally guided incremental docking strategy that combined homology modeling, protein-protein docking and refinement by means of molecular dynamics simulations. The structural features of the in silico model allowed us to identify the regions that mediate the recognition between the interacting proteins, revealing the active role of the ubiquitin crosslinked to E1 in the complex formation. Finally, the role of these regions involved in the E1-E2 binding was validated by designing short peptides that specifically interfere with the binding of UbcH10, thus supporting the reliability of the proposed model and representing valuable scaffolds for the design of peptidomimetic compounds that can bind selectively to Ubcs and inhibit the ubiquitylation process in pathological disorders.PLoS ONE 11/2014; 9(11):e112082. DOI:10.1371/journal.pone.0112082 · 3.53 Impact Factor
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ABSTRACT: UbcH10 is an important regulator for the mitotic spindle assembly checkpoint pathway that regulates cell-cycle progression. Overexpression of UbcH10 significantly correlated with advanced tumor grade and high cell proliferation. The expression of UbcH10 and Ki-67 in meningioma tissues were evaluated immunohistochemically in 47 patients with meningiomas. The correlation of UbcH10 immunoreactivity with clinicopathological features and the prognostic value of UbcH10 in patients were also analyzed. Immunohistochemistry showed an increase in UbcH10 labeling index in atypical and anaplastic meningiomas versus classical meningiomas (10.53 ± 5.79% vs. 4.23 ± 2.85%, P < 0.001). There was a positive correlation between UbcH10 and Ki-67 immunoreactivity (Spearman r = 0.77, P < 0.001). Clinicopathological evaluation suggested that UbcH10 expression was associated with tumor grade and recurrence (P < 0.05). Kaplan-Meier survival analysis and Cox multivariate analysis revealed a significant correlation between high levels of UbcH10 immunoreactivity and high rates of tumor recurrence. We conclude that UbcH10 may play important roles in the development of meningioma, high UbcH10 labeling index indicates higher grade of meningioma, and UbcH10 may be a useful molecular marker for predicting the prognosis of meningioma.Journal of Surgical Oncology 09/2012; 106(3):327-31. DOI:10.1002/jso.22141 · 2.84 Impact Factor