The emerging role of APC/CCdh1 in controlling differentiation, genomic stability and tumor suppression.
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.
Wäsch
R
R
Department of Hematology and Oncology, University Medical Center, Freiburg, Germany. ralph.waesch@uniklinik-freiburg.de
Robbins
J A
JA
Cross
F R
FR
D064173:Anaphase-Promoting Complex-Cyclosome; D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D042822:Genomic Instability; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D043743:Ubiquitin-Protein Ligase Complexes / Q000378:metabolism*
D018797:Cell Cycle Proteins; D043743:Ubiquitin-Protein Ligase Complexes; D064173:Anaphase-Promoting Complex-Cyclosome