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Targeting Mitotic Exit in Malignant Cells.
Methods Mol Biol
November 2024
Faculty of Medicine, Department of Medicine I, Medical Center, University of Freiburg, Freiburg, Germany.
In order to sustain genomic stability by correct DNA replication and mitosis and thus avoid malignant transformation of cells, the cell cycle is a strictly regulated process. Aberrant cell cycle regulation and defects in mitosis in malignant cells are targets of various cancer therapies. Cancer cells may survive antimitotic treatment due to mitotic slippage with a residual activity of the ubiquitin ligase anaphase-promoting complex (APC/C) and a continuous slow ubiquitin-proteasome-dependent cyclin B-degradation leading to mitotic exit.
View Article and Find Full Text PDFAPC/C prevents a noncanonical order of cyclin/CDK activity to maintain CDK4/6 inhibitor-induced arrest.
Proc Natl Acad Sci U S A
July 2024
Curriculum in Genetics and Molecular Biology, The University of North Carolina at Chapel Hill, Chapel Hill, NC 27599.
Article Synopsis
- Regulated cell cycle progression is crucial for maintaining cellular balance and preventing cancer, with the E3 ubiquitin ligase APC/C playing a key role in preventing premature entry into the S phase for proliferating cells.
- Research shows that APC/C activity is necessary for maintaining cell cycle arrest when CDK4/6 is inhibited, indicating that protein degradation is vital for effective cell cycle regulation.
- The study suggests that cancers with high levels of EMI1 may evade CDK4/6 inhibition, leading to unregulated S phase entry and increased genome instability due to improper licensing of DNA replication.
Molecular Regulation of Porcine Skeletal Muscle Development: Insights from Research on CDC23 Expression and Function.
Int J Mol Sci
March 2024
Key Laboratory of Swine Genetics and Breeding of the Ministry of Agriculture, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Cell division cycle 23 (CDC23) is a component of the tetratricopeptide repeat (TPR) subunit in the anaphase-promoting complex or cyclosome (APC/C) complex, which participates in the regulation of mitosis in eukaryotes. However, the regulatory model and mechanism by which the CDC23 gene regulates muscle production in pigs are largely unknown. In this study, we investigated the expression of CDC23 in pigs, and the results indicated that CDC23 is widely expressed in various tissues and organs.
View Article and Find Full Text PDFRegulated cell cycle progression ensures homeostasis and prevents cancer. In proliferating cells, premature S phase entry is avoided by the E3 ubiquitin ligase APC/C (anaphase promoting complex/cyclosome), although the APC/C substrates whose degradation restrains G1-S progression are not fully known. The APC/C is also active in arrested cells that exited the cell cycle, but it is not clear if APC/C maintains all types of arrest.
View Article and Find Full Text PDFTargeting Cdc20 for cancer therapy.
Biochim Biophys Acta Rev Cancer
November 2022
Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; Lung Cancer Research Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea. Electronic address:
The Anaphase-Promoting Complex/Cyclosome (APC/C), an E3 ubiquitin ligase, and two co-activators, Cdc20 and Cdh1, enable the ubiquitin-dependent proteasomal degradation of various critical cell cycle regulators and govern cell division in a timely and precise manner. Dysregulated cell cycle events cause uncontrolled cell proliferation, leading to tumorigenesis. Studies have shown that Cdh1 has tumor suppressive activities while Cdc20 has an oncogenic property, suggesting that Cdc20 is an emerging therapeutic target for cancer treatment.
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