The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression

• Published in: Oncogene Vol. 29; no. 1; pp. 1 - 10
• Main Authors: Wäsch, R, Robbins, J A, Cross, F R
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 07.01.2010; Nature Publishing Group
• Subjects: Anaphase-Promoting Complex-Cyclosome; Animals; Apoptosis; Biological and medical sciences; Cell Biology; Cell cycle; Cell Cycle - physiology; Cell Cycle Proteins - metabolism; Cell Cycle Proteins - physiology; Cell cycle, cell proliferation; Cell Differentiation - physiology; Cell physiology; Cell Proliferation; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cellular biology; Deoxyribonucleic acid; Diverse techniques; DNA; Fundamental and applied biological sciences. Psychology; Genomic Instability; Genomics; Human Genetics; Humans; Internal Medicine; Medicine; Medicine & Public Health; Models, Biological; Molecular and cellular biology; Neoplasms - genetics; Neoplasms - pathology; Neoplasms - physiopathology; Oncology; review; Ubiquitin-Protein Ligase Complexes - metabolism; tumor suppression; proteasome; anaphase-promoting complex; differentiation; genomic instability; ubiquitin; Ubiquitin; Multicatalytic endopeptidase complex; Stability; Carbon-nitrogen ligases; Enzyme; Genomics; Suppression; Carcinogenesis; Peptidases; Ligases; Cell cycle; Hydrolases; Instability; Tumor; Differentiation; Ubiquitin-protein ligase
• ISSN: 0950-9232; 1476-5594; 1476-5594
• DOI: 10.1038/onc.2009.325

Deregulation of the G1/G0 phase of the cell cycle can lead to cancer. During G1, most cells commit alternatively to DNA replication and division, or to cell-cycle exit and differentiation. The anaphase-promoting complex or cyclosome (APC/C) activated by Cdh1 coordinately eliminates positive cell-cycle regulators as well as inhibitors of differentiation, thereby coupling cell-cycle exit and differentiation. Misregulation of Cdh1 thus has the potential to promote both cell-cycle re-entry and either perturbed differentiation or dedifferentiation. In addition, APC/C Cdh1 is required to maintain genomic stability. As a result, loss of Cdh1 can contribute to tumorigenesis in the form of proliferation of poorly differentiated and genetically unstable cells.