TY - JOUR
T1 - Ubiquitin ligases
T2 - Cell-cycle control and cancer
AU - Nakayama, Keiichi I.
AU - Nakayama, Keiko
N1 - Funding Information:
The authors wish to thank all members of our laboratories for their comments. We are also thankful to A. Ohta and M. Kimura for help in preparing this manuscript. This research was partly supported by a grant from CREST, Japan Science and Technology Agency.
PY - 2006/5
Y1 - 2006/5
N2 - A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.
AB - A driving force of the cell cycle is the activation of cyclin-dependent kinases (CDKs), the activities of which are controlled by the ubiquitin-mediated proteolysis of key regulators such as cyclins and CDK inhibitors. Two ubiquitin ligases, the SKP1-CUL1-F-box-protein (SCF) complex and the anaphase-promoting complex/cyclosome (APC/C), are responsible for the specific ubiquitylation of many of these regulators. Deregulation of the proteolytic system might result in uncontrolled proliferation, genomic instability and cancer. Cumulative clinical evidence shows alterations in the ubiquitylation of cell-cycle regulators in the aetiology of many human malignancies. A better understanding of the ubiquitylation machinery will provide new insights into the regulatory biology of cell-cycle transitions and the development of anti-cancer drugs.
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U2 - 10.1038/nrc1881
DO - 10.1038/nrc1881
M3 - Review article
C2 - 16633365
AN - SCOPUS:33646345376
SN - 1474-175X
VL - 6
SP - 369
EP - 381
JO - Nature Reviews Cancer
JF - Nature Reviews Cancer
IS - 5
ER -
