The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis

Prinz, Susanne; Hwang, Ellen S.; Visintin, Rosella; Amon, Angelika

doi:10.1016/s0960-9822(98)70298-2

Cited by 218 publications

(233 citation statements)

References 47 publications

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“…Full activation of APC Cdh1 arises by a lowering of overall Cdk activity through APC Cdc20 activity and release of Cdc14 phosphatase through the mitotic exit network and associated pathways (Visintin et al, 1999;Stegmeier et al, 2002). Furthermore, to smooth the transition from APC Cdc20 to APC Cdh1 , APC Cdh1 is able to mediate the destruction of APC Cdc20 in late mitosis (Prinz et al, 1998;Shirayama et al, 1998). Targeted proteolysis thus reinforces the feedback loop that ultimately raises APC Cdh1 levels over that of APC Cdc20 Peters, 2002).…”

Section: Iκkα and Iκkβmentioning

confidence: 98%

SCF-mediated protein degradation and cell cycle control

2005

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The regulatory step in ubiquitin (Ub)-mediated protein degradation involves recognition and selection of the target substrate by an E3 Ub-ligase. E3 Ub-ligases evoke sophisticated mechanisms to regulate their activity temporally and spatially, including multiple post-translational modifications, combinatorial E3 Ub-ligase pathways, and subcellular localization. The phosphodegrons of many substrates incorporate the activities of multiple kinases, and ubiquitination only occurs when all necessary phosphorylation signals have been incorporated. In this manner, the precise timing of degradation can be controlled. Another way that the Ub pathway tightly controls the timing of proteolysis is with multiple E3 Ubligases acting upon a single target. Lastly, subcellular localization can either promote or prevent degradation by regulating the accessibility of kinases and E3 Ub-ligases. This review highlights recent findings that exemplify these emerging themes in the regulation of E3 Ub-ligase substrate recognition.

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Section: Iκkα and Iκkβmentioning

confidence: 98%

SCF-mediated protein degradation and cell cycle control

2005

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“…The affinity of activators of the APC is regulated by phosphorylation of APC subunits (Kotani et al, 1999;Kramer et al, 2000;Kraft et al, 2003). Cdc20 activity is regulated by transcription and APC Cdh1 -dependent degradation leading to APC Cdc20 activity from early mitosis until the M to G1 transition (Fang et al, 1998b;Prinz et al, 1998;Shirayama et al, 1998;Pfleger and Kirschner, 2000;Huang et al, 2001). Cdk1 and MAPK can phosphorylate Cdc20; although it is controversial whether phosphorylation of Cdc20 is necessary for APC activation in human cells (Kotani et al, 1999;Kramer et al, 2000;Yudkovsky et al, 2000), it is required for its inhibition by the spindle checkpoint (Chung and Chen, 2003).…”

Section: Regulation Of Apc Activitymentioning

confidence: 99%

“…Initially it has been reported that the protein level of Cdh1 remains relatively constant throughout the cell cycle (Fang et al, 1998b;Prinz et al, 1998) and Cdh1 is activated by dephosphorylation from the M to G1 transition until the end of the G1 phase Jaspersen et al, 1999;Lukas et al, 1999;Kramer et al, 2000). However, there are also reports that Cdh1 levels oscillate during the cell cycle at least in human cells Hsu et al, 2002).…”

Section: Regulation Of Apc Activitymentioning

confidence: 99%

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

2005

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“…Under normal conditions, the anaphase-promoting complex/cyclosome (APC/C) 1 promotes the ubiquitination of Pds1, leading to its degradation, and consequently the activation of Esp1 (13,14). The ability of the APC/C to ubiquitinate Pds1 depends on the physical association between Pds1 and an APC/C-associated protein, Cdc20 (15)(16)(17)(18). Specifically, abolishing the binding of Pds1 to Cdc20 prevents Pds1 ubiquitination (17,18).…”

mentioning

confidence: 99%

“…Specifically, abolishing the binding of Pds1 to Cdc20 prevents Pds1 ubiquitination (17,18). Cdc20, and its homolog Cdh1, belong to a family of WD-repeat proteins that confer substrate specificity to the APC/C (15,16). Cdc20 is active early in mitosis and is involved in the ubiquitination of several cell cycle regulators, including Pds1 and the cyclins Clb5 and Clb2 (19 -21).…”

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confidence: 99%

Two Distinct Pathways for Inhibiting Pds1 Ubiquitination in Response to DNA Damage

Agarwal

Tang

et al. 2003

Journal of Biological Chemistry

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The presence of DNA damage activates a conserved cellular response known as the DNA damage checkpoint pathway. This pathway induces a cell cycle arrest that persists until the damage is repaired. Consequently, the failure to arrest in response to DNA damage is associated with genomic instability. In budding yeast, activation of the DNA damage checkpoint pathway leads to a mitotic cell cycle arrest. Following the detection of DNA damage, the checkpoint signal is transduced via the Mec1 kinase, which in turn activates two kinases, Rad53 and Chk1 that act in parallel pathways to bring about the cell cycle arrest. The downstream target of Rad53 is unknown. The target of Chk1 is Pds1, an inhibitor of anaphase initiation whose degradation is a prerequisite for mitotic progression. Pds1 degradation is dependent on its ubiquitination by the anaphase-promoting complex/cyclosome ubiquitin ligase, acting in conjunction with the Cdc20 protein (APC/C Cdc20 ). Previous studies showed that the Rad53 and Chk1 pathways independently lead to Pds1 stabilization but the mechanism for this was unknown. In the present study we show that both the Chk1 and the Rad53 pathways inhibit the APC/ C Cdc20 -dependent ubiquitination of Pds1 but they affect different steps of the process: the Rad53 pathway inhibits the Pds1-Cdc20 interaction whereas Chk1-dependent phosphorylation of Pds1 inhibits the ubiquitination reaction itself. Finally, we show that once the DNA damage is repaired, Pds1 dephosphorylation is involved in the recovery from the checkpoint induced cell cycle arrest.

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The regulation of Cdc20 proteolysis reveals a role for the APC components Cdc23 and Cdc27 during S phase and early mitosis

Abstract: There are remarkable differences in the regulation of Cdc20 and Cdh1/Hct1. Furthermore, the APC activator Cdc20 is itself a substrate of the Cdc27 have a role in the degradation of Cdc20 during S Phase and early mitosis that is not mediated by its destruction box.

Cited by 218 publications

References 47 publications

SCF-mediated protein degradation and cell cycle control

SCF-mediated protein degradation and cell cycle control

Anaphase-promoting complex-dependent proteolysis of cell cycle regulators and genomic instability of cancer cells

Two Distinct Pathways for Inhibiting Pds1 Ubiquitination in Response to DNA Damage

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