How Proteolysis Drives the Cell Cycle

Randall W. King; Raymond J. Deshaies; Jan‐Michael Peters; Marc W. Kirschner

doi:10.1126/science.274.5293.1652

Abstract

Oscillations in the activity of cyclin-dependent kinases (CDKs) promote progression through the eukaryotic cell cycle. This review examines how proteolysis regulates CDK activity—by degrading CDK activators or inhibitors—and also how proteolysis may directly trigger the transition from metaphase to anaphase. Proteolysis during the cell cycle is mediated by two distinct ubiquitin-conjugation pathways. One pathway, requiring CDC34, initiates DNA replication by degrading a CDK inhibitor. The second pathway, involving a large protein complex called the anaphase-promoting complex or cyclosome, initiates chromosome segregation and exit from mitosis by degrading anaphase inhibitors and mitotic cyclins. Proteolysis therefore drives cell cycle progression not only by regulating CDK activity, but by directly influencing chromosome and spindle dynamics.

Keywords

Cell biologyCyclin-dependent kinaseProteolysisCell cycleMitosisAnaphaseAnaphase-promoting complexBiologyCell division control protein 4Restriction pointPolo-like kinaseCDK inhibitorMetaphaseCyclin BCyclinUbiquitinCellBiochemistryChromosomeUbiquitin ligase

Affiliated Institutions

Related Publications

Dominant-negative cyclin-selective ubiquitin carrier protein E2-C/UbcH10 blocks cells in metaphase

Fiona M. Townsley , A Aristarkhov , S. Mey-Tal Beck +2 more

Destruction of mitotic cyclins by ubiquitin-dependent proteolysis is required for cells to complete mitosis and enter interphase of the next cell cycle. In clam eggs, this proce...

1997 Proceedings of the National Academy o... 220 citations

A Ubiquitin-Conjugating Enzyme in Fission Yeast That Is Essential for the Onset of Anaphase in Mitosis

Fumio Osaka , Hiroaki Seino , Takeshi Seno +1 more

A cDNA encoding a ubiquitin-conjugating enzyme designated UbcP4 in fission yeast was isolated. Disruption of its genomic gene revealed that it was essential for cell viability. ...

1997 Molecular and Cellular Biology 49 citations

Association of the Cyclin-dependent Kinases and 14-3-3 Sigma Negatively Regulates Cell Cycle Progression

Christine Laronga , Heng-Yin Yang , Christopher L. Neal +1 more

14-3-3 sigma, implicated in cell cycle arrest by p53, was cloned by expression cloning through cyclin-dependent kinase 2 (CDK2) association. 14-3-3 sigma shares cyclin-CDK2 bind...

2000 Journal of Biological Chemistry 306 citations

E2-C, a cyclin-selective ubiquitin carrier protein required for the destruction of mitotic cyclins.

A Aristarkhov , E Eytan , Akshata Moghe +3 more

Ubiquitin-dependent proteolysis of the mitotic cyclins A and B is required for the completion of mitosis and entry into the next cell cycle. This process is catalyzed by the cyc...

1996 Proceedings of the National Academy o... 138 citations

Phosphorylation of Human MAD1 by the BUB1 Kinasein Vitro

Todd Seeley , Ling Wang , Julia Y. Zhen

The BUB/MAD signaling pathway monitors attachment of chromosomes to spindle poles in mitotic cells. Mutations of the human BUB1 locus were identified in cancer cells exhibiting ...

1999 Biochemical and Biophysical Research ... 46 citations

Publication Info

Year: 1996
Type: review
Volume: 274
Issue: 5293
Pages: 1652-1659
Citations: 1275
Access: Closed

External Links

View on DOI.org

Social Impact

Altmetric

How Proteolysis Drives the Cell Cycle

PlumX Metrics

Social media, news, blog, policy document mentions

Citation Metrics

1275

OpenAlex

Cite This

APA Style

                            
                                
                                    Randall W. King, 
                                
                                    Raymond J. Deshaies, 
                                
                                    Jan‐Michael Peters
                                
                                et al.
                            
                            (1996). 
                            How Proteolysis Drives the Cell Cycle. 
                            Science
                            , 274
                            (5293)
                            , 1652-1659.
                            https://doi.org/10.1126/science.274.5293.1652
                        

Identifiers

DOI: 10.1126/science.274.5293.1652