Abstract
In the present chapter we discuss the essential roles of the human E3 ubiquitin ligase Anaphase Promoting Complex/Cyclosome (APC/C) in mitosis as well as the emerging evidence of important APC/C roles in cellular processes beyond cell division control such as regulation of genomic integrity and cell differentiation of the nervous system. We consider the potential incipient role of APC/C dysregulation in the pathophysiology of the neurological disorder Alzheimer’s disease (AD). We also discuss how certain Deoxyribonucleic Acid (DNA) and Ribonucleic Acid (RNA) viruses take control of the host’s cell division regulatory system through harnessing APC/C ubiquitin ligase activity and hypothesise the plausible molecular mechanisms underpinning virus manipulation of the APC/C. We also examine how defects in the function of this multisubunit protein assembly drive abnormal cell proliferation and lastly argue the potential of APC/C as a promising therapeutic target for the development of innovative therapies for the treatment of chronic malignancies such as cancer.
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Abbreviations
- Aβ:
-
Amyloid beta
- Ad:
-
Adenovirus
- AD:
-
Alzheimer’s disease
- ADM:
-
Adriamycin
- AML:
-
Acute Myeloid Leukemia
- APC/C:
-
Anaphase Promoting Complex/Cyclosome
- ATL:
-
Adult T-cell Leukaemia/Lymphoma
- ATP:
-
Adenosine Triphosphate
- ATR:
-
Ataxia Telangiectasia and Rad3-related protein
- Bard1:
-
BRCA1-associated RING domain protein 1
- BRSK2:
-
Brain-Specific Kinase 2
- Bub1:
-
Budding uninhibited by benzimidazoles 1
- Bub3:
-
Budding uninhibited by benzimidazoles 3
- BubR1:
-
Budding uninhibited by benzimidazoles Related 1
- CAV:
-
Chicken Anemia Virus
- CAV-Apoptin:
-
Chicken Anemia Virus-Apoptin
- CBP:
-
Cyclic AMP response element Binding Protein
- Cdc5:
-
Cell division cycle 5
- Cdc6:
-
Cell division cycle 6
- Cdc7:
-
Cell division cycle 7
- Cdc20:
-
Cell division cycle 20
- Cdc23:
-
Cell division cycle 23
- Cdc26:
-
Cell division cycle 26
- Cdc27:
-
Cell division cycle 27
- Cdc42:
-
Cell division cycle 42
- Cdc55:
-
Cell division cycle 55
- CDDP :
-
Cisplatin
- Cdh1:
-
Cadherin 1
- Cdk:
-
Cyclin-dependent kinase
- Cdk1:
-
Cyclin-dependent kinase 1
- Cdk4:
-
Cyclin-dependent kinase 4
- Cdk5:
-
Cyclin-dependent kinase 5
- Cdt1:
-
Chromatin licensing and DNA replication factor 1
- CENP-E:
-
Centromere-associated Protein E
- CENP-F:
-
Centromere-associated Protein F
- Chk1:
-
Checkpoint kinase 1
- Cik1:
-
Chromosome instability and karyogamy protein 1
- CK1:
-
Casein Kinase 1
- CK1δ:
-
Casein Kinase 1 delta
- CKAP2:
-
Cytoskeleton-Associated Protein 2
- cKO:
-
conditional Knockout
- Cks1:
-
Cyclin-dependent kinases regulatory subunit 1
- CNS:
-
Central Nervous System
- co-IP:
-
co-Immunoprecipitation
- CPC:
-
Chromosomal Passenger Complex
- cryo-EM :
-
cryogenic Electron Microscopy
- D-box:
-
Destruction box
- DDB1:
-
Damaged DNA Binding protein 1
- DNA :
-
Deoxyribonucleic Acid
- dNTPS:
-
deoxyribonucleotide Triphosphate
- dTTP:
-
deoxythymidine Triphosphate
- E:
-
Early
- E1A:
-
Adenovirus Early region 1A
- E2F1:
-
E2F Transcription Factor 1
- E2F3:
-
E2F Transcription Factor 3
- E4orf4:
-
Early region 4 open reading frame 4
- EAA:
-
Excitatory Amino Acid
- Ect2:
-
Epithelial cell transforming 2
- EHMT2:
-
Euchromatic Histone Lysine Methyltransferase 2
- EM:
-
Electron Microscopy
- Emi1:
-
Early mitotic inhibitor
- ER:
-
Endoplasmic Reticulum
- EYA1:
-
Eyes Absent 1
- FAN1:
-
FANCD2-Associated Nuclease 1
- Fin1:
-
Filaments in between nuclei protein 1
- FoxM1:
-
Forkhead box M1
- Fzr:
-
Fizzy-related protein homolog
- G1:
-
Gap 1
- G2:
-
Gap 2
- G6PD:
-
Glucose-6-Phosphate Dehydrogenase
- GCPs:
-
Granule Cell Progenitors
- GLP:
-
Glucagon-Like Peptide
- GLP1:
-
Glucagon-Like Peptide-1
- GLS1:
-
Glutaminase 1
- GluR1 :
-
Glutamate Receptor 1
- GSCs:
-
Glioblastoma Stem-like Cells
- GSH:
-
Glutathione
- GSSG:
-
Glutathione disulfide
- HAd:
-
Human Adenovirus
- HBV:
-
Hepatitis B Virus
- HCC:
-
Hepatocellular Carcinoma
- HCMV:
-
Human Cytomegalovirus
- HECT:
-
Homologous to the E6-AP Carboxyl Terminus
- HGyv-Apoptin:
-
Human Gyrovirus-Apoptin
- Hmmr:
-
Hyaluronan-mediated motility receptor
- HPV:
-
Human Papillomaviruses
- Hsl1 from yeast:
-
Histone synthetic lethal 1
- HTLV-1:
-
Human T-cell Lymphotropic Virus type 1
- HURP:
-
Hepatoma Up-Regulated Protein
- Id1:
-
Inhibitor of differentiation 1
- Id2:
-
Inhibitor of differentiation 2
- IE:
-
Intermediate Early
- IE72:
-
Intermediate protein 72
- IE86:
-
Intermediate protein 86
- IQGAP:
-
IQ motif containing GTPase-Activating Protein 1
- IR:
-
Isoleucine Arginine
- JAK:
-
Janus Kinase
- JNK:
-
C-Jun N-terminal Kinase
- kDa:
-
kiloDalton
- Kif18A:
-
Kinesin family member 18A
- Knl1:
-
Kinetochore scaffold 1
- L:
-
Late
- LT:
-
Large T antigen
- LTP:
-
Long-Term Potentiation
- M :
-
Mitosis
- Mad1:
-
Mitotic arrest deficient 1
- Mad2:
-
Mitotic arrest deficient 2
- MAPK:
-
Mitogen-Activated Protein Kinase
- MCC:
-
Mitotic Checkpoint Complex
- MCPH1:
-
Microcephalin-1
- MDC1:
-
Mediator DNA Damage Checkpoint 1
- MEFs:
-
Mouse Embryonic Fibroblasts
- MgcRacGAP:
-
Male germ cell RacGTPase Activating Protein
- MOAP-1:
-
Modulator of Apoptosis Protein 1
- Mps1:
-
Monopolar spindle 1
- mRNA:
-
messenger RNA
- NADPH:
-
Nicotinamide Adenine Dinucleotide Phosphate
- Nek2A:
-
NIMA-related kinase 2A
- NeuroD2:
-
Neurogenic Differentiation factor 2
- NFT:
-
Neurofibrillary Tangles
- NIPA:
-
Nuclear Interaction Partner of Alk kinase
- Nlp:
-
Ninein-like protein
- NMDARs:
-
N-methyl-D-aspartate Receptors
- NPCs:
-
Neural Progenitor Cells
- NS5A:
-
Nonstructural protein 5A
- NuSAP:
-
Nucleolar Spindle–Associated Protein
- ORFV:
-
Orf Virus
- p21Cip1:
-
Cyclin dependent kinase inhibitor 1
- p27Kip1:
-
Cyclin dependent kinase inhibitor 1B
- PDAC:
-
Pancreatic Ductal Adenocarcinoma
- Pds1:
-
Premature dissociation of sisters
- PFKFB3 :
-
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase isoform 3
- Plk1:
-
Polo-like kinase 1
- PML bodies:
-
Promyelocytic Leukaemia bodies
- PP2a:
-
Protein Phosphatase 2
- PPP:
-
Pentose-Phosphate Pathway
- pRb:
-
Retinoblastoma protein
- proTAME:
-
pro-tosyl-l-arginine methyl ester
- PSD:
-
Postsynaptic Density
- Rac1:
-
Ras-related C3 botulinum toxin substrate 1
- RAP80:
-
Receptor-Associated Protein 80
- Rassf1a:
-
Ras association domain containing family 1 isoform a
- RbX1:
-
RING-box protein 1
- RbX2:
-
RING-box protein 2
- RhoA:
-
Ras homolog gene family member A
- RING:
-
Really Interesting New Gene
- RNA :
-
Ribonucleic Acid
- RNAi:
-
RNA interference
- Rock2:
-
Rho protein kinase 2
- ROS:
-
Reactive Oxygen Species
- S:
-
Synthesis
- SAC :
-
Spindle Assembly Checkpoint
- S. cerevisiae :
-
Saccharomyces cerevisiae
- SCF:
-
Skp1-Cullin-1-F-box protein
- Sgo1:
-
Shugoshin 1
- Shank:
-
SH3 and multiple ankyrin repeat domains protein
- siRNA:
-
small interfering RNA
- Six1:
-
Sineoculis homeobox homolog 1
- Skp1:
-
S-phase-kinase-associated protein 1
- Skp2:
-
S-phase kinase-associated protein 2
- SnoN:
-
Ski-related novel protein N
- SPOP:
-
Speckle-type POZ Protein
- STAT:
-
Signal Transducer and Activator of Transcription
- SV40:
-
Simian Virus 40
- TACC3:
-
Transforming Acidic Coiled-Coil protein 3
- TAME:
-
Tosyl-l-arginine methyl ester
- TGCTs:
-
Testicular Germ Cell Tumours
- TGF-β:
-
Transforming Growth Factor beta
- TK1:
-
Thymidine Kinase
- TMPK:
-
Thymidylate Protein Kinase
- TNM:
-
TNM classification of malignant tumors
- TPR:
-
Tetratricopeptide Repeat
- Tpx2:
-
Targeting protein for Xklp2
- TRB3:
-
Tribbles homolog 3
- TRRAP:
-
Transformation/Transcription domain-Associated protein
- Tyc1:
-
Tiny yeast comet 1
- Ube2C:
-
Ubiquitin-conjugating enzyme E2 C
- Ube2D:
-
Ubiquitin-conjugating enzyme E2 D2
- UPS1:
-
Ubiquitin carboxyl-terminal hydrolase 1
- USP37:
-
Ubiquitin Specific-processing Protease 37
- WES:
-
Whole-Exome Sequencing
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Curtis, N.L., Bolanos-Garcia, V.M. (2019). The Anaphase Promoting Complex/Cyclosome (APC/C): A Versatile E3 Ubiquitin Ligase. In: Harris, J., Marles-Wright, J. (eds) Macromolecular Protein Complexes II: Structure and Function . Subcellular Biochemistry, vol 93. Springer, Cham. https://doi.org/10.1007/978-3-030-28151-9_18
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