Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

Alfieri, Claudio; Zhang, Suyang; Barford, David

doi:10.1098/rsob.170204

Cited by 157 publications

(198 citation statements)

References 262 publications

(674 reference statements)

Supporting

Mentioning

195

Contrasting

Unclassified

Order By: Relevance

“…However, these E3s employ sets of interchangeable substrate receptors for distinct regulation (Alfieri et al, 2017;Lydeard et al, 2013;Watson et al, 2019). Thus, we hypothesized that other GID substrate receptor(s) may exist, and identified the ORF YGR066C as encoding a protein displaying homology to Gid4, including the Gid5-binding hydrophobic stripe and C-terminal anchor ( Figure S4C).…”

Section: A Family Of Related Gid E3smentioning

confidence: 99%

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Qiao

Langlois

Chrustowicz

et al. 2019

Preprint

View full text Add to dashboard Cite

Qiao et al. (Schulman) -Interconversion between anticipatory and active GID E3 ubiquitin ligase conformations via metabolically-driven substrate receptor assembly 2 SUMMARY Cells respond to environmental changes by toggling metabolic pathways, preparing for homeostasis, and anticipating future stresses. For example, in Saccharomyces cerevisiae, carbon stress-induced gluconeogenesis is terminated upon glucose availability, a process that involves the multiprotein E3 ligase, GID SR4 , recruiting N-termini and catalyzing ubiquitylation of gluconeogenic enzymes. Here, genetics, biochemistry, and cryo electron microscopy define molecular underpinnings of glucose-induced degradation. Unexpectedly, carbon stress induces an inactive anticipatory complex (GID Ant ), which awaits a glucoseinduced substrate receptor to form the active GID SR4 . Meanwhile, other environmental perturbations elicit production of an alternative substrate receptor assembling into a related E3 ligase complex. The intricate structure of GID Ant enables anticipating and ultimately binding various N-degron targeting (i.e. "N-end rule") substrate receptors, while the GID SR4 E3 forms a clamp-like structure juxtaposing substrate lysines with the ubiquitylation active site. The data reveal evolutionarily conserved GID complexes as a family of multisubunit E3 ubiquitin ligases responsive to extracellular stimuli.

show abstract

Section: A Family Of Related Gid E3smentioning

confidence: 99%

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Qiao

Langlois

Chrustowicz

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…Cyclin-dependent kinases (Cdks) and the APC/C are some of the most significant cell cycle regulators, controlling the cell cycle through phosphorylation and ubiquitylation, respectively [1][2][3][4]. At the same time, growth, proliferation and differentiation are controlled accordingly in response to environmental cues, ensuring genome stability.…”

Section: Introductionmentioning

confidence: 99%

PP2A‐B56 binds to Apc1 and promotes Cdc20 association with the APC/C ubiquitin ligase in mitosis

Fujimitsu

Yamano

2019

EMBO Reports

View full text Add to dashboard Cite

Cell cycle progression and genome stability are regulated by a ubiquitin ligase, the anaphase-promoting complex/cyclosome (APC/C). Cyclin-dependent kinase 1 (Cdk1) has long been implicated in APC/ C activation; however, the molecular mechanisms of governing this process in vivo are largely unknown. Recently, a Cdk1-dependent phosphorylation relay within Apc3-Apc1 subunits has been shown to alleviate Apc1-mediated auto-inhibition by which a mitotic APC/ C co-activator Cdc20 binds to and activates the APC/C. However, the underlying mechanism for dephosphorylation of Cdc20 and APC/C remains elusive. Here, we show that a disordered loop domain of Apc1 (Apc1-loop 500 ) directly binds the B56 regulatory subunit of protein phosphatase 2A (PP2A) and stimulates Cdc20 loading to the APC/C. Using the APC/C reconstitution system in Xenopus egg extracts, we demonstrate that mutations in Apc1loop 500 that abolish B56 binding decrease Cdc20 loading and APC/ C-dependent ubiquitylation. Conversely, a non-phosphorylatable mutant Cdc20 can efficiently bind the APC/C even when PP2A-B56 binding is impeded. Furthermore, PP2A-B56 preferentially dephosphorylates Cdc20 over the Apc1 inhibitory domain. These results indicate that Apc1-loop 500 plays a role in dephosphorylating Cdc20, promoting APC/C-Cdc20 complex formation in mitosis.

show abstract

“…Genes involved in DNA replication include, among others, DNA polymerase epsilon catalytic subunit (Cre03.g179961, light green circle) (Henninger and Pursell, 2014), the origin recognition complex subunit 4 (Cre17.g726500, yellow square) (Li et al, 2018) and DNA primase (Cre06.g293000, purple square) (Guilliam et al, 2015). Genes involved in cell division include gamma tubulin complex 4 (Cre01.g019150, beige diamond) (Janke, 2014), anaphase-promoting complex subunit 6 (Cre13.g562950, light blue circle) (Alfieri et al, 2017) and sister-chromatid cohesion protein 3 (Cre17.g736400, orange circle) (Losada, 2008).…”

Section: Cell Division Is Synchronized By Light In Algaementioning

confidence: 99%

Diurnal.plant.tools: comparative transcriptomic and co-expression analyses of diurnal gene expression of the Archaeplastida kingdom

Tan

Ferrari

et al. 2019

Preprint

View full text Add to dashboard Cite

Almost all organisms coordinate some aspects of their biology through the diurnal cycle. Photosynthetic organisms, and plants especially, have established complex programs that coordinate physiological, metabolic and developmental processes with the changing light. The diurnal regulation of the underlying transcriptional processes is observed when groups of functionally related genes (gene modules) are expressed at a specific time of the day. However, studying the diurnal regulation of these gene modules in the plant kingdom was hampered by the large amount of data required for the analyses. To meet this need, we used gene expression data from 17 diurnal studies spanning the whole Archaeplastida kingdom (Plantae kingdom in the broad sense) to make an online diurnal database. We have equipped the database with tools that allow user-friendly cross-species comparisons of gene expression profiles, entire co-expression networks, co-expressed clusters (involved in specific biological processes), time-specific gene expression, and others. We exemplify how these tools can be used by studying three important biological questions: (i) the evolution of cell division, (ii) the diurnal control of gene modules in algae and (iii) the conservation of diurnally-controlled modules across species. The database is freely available at http://diurnal.plant.tools/.

show abstract

Visualizing the complex functions and mechanisms of the anaphase promoting complex/cyclosome (APC/C)

Cited by 157 publications

References 262 publications

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

Interconversion between Anticipatory and Active GID E3 Ubiquitin Ligase Conformations via Metabolically Driven Substrate Receptor Assembly

PP2A‐B56 binds to Apc1 and promotes Cdc20 association with the APC/C ubiquitin ligase in mitosis

Diurnal.plant.tools: comparative transcriptomic and co-expression analyses of diurnal gene expression of the Archaeplastida kingdom

Contact Info

Product

Resources

About