| CDC27 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Identifiers | |||||||||||||||||||||||||||||||||||||||||||||||||||
| Aliases | CDC27 , ANAPC3, APC3, CDC27Hs, D0S1430E, D17S978E, H-NUC, HNUC, NUC2, cell division cycle 27 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 116946; MGI: 102685; HomoloGene: 960; GeneCards: CDC27; OMA:CDC27 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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| Wikidata | |||||||||||||||||||||||||||||||||||||||||||||||||||
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Cell division cycle protein 27 homolog is a protein that in humans is encoded by the CDC27 gene. [5] [6]
The protein encoded by this gene shares strong similarity with Saccharomyces cerevisiae protein Cdc27, and the gene product of Schizosaccharomyces pombe nuc 2. This protein is a component of anaphase-promoting complex (APC), which is composed of eight protein subunits and highly conserved in eucaryotic cells. APC catalyzes the formation of cyclin B-ubiquitin conjugate that is responsible for the ubiquitin-mediated proteolysis of B-type cyclins. This protein and 3 other members of the APC complex contain the TPR (tetratricopeptide repeat), a protein domain important for protein-protein interaction. This protein was shown to interact with mitotic checkpoint proteins including Mad2, p55CDC and BUBR1, and thus may be involved in controlling the timing of mitosis. [6]
CDC27 has been shown to interact with:
Anaphase-promoting complex is an E3 ubiquitin ligase that marks target cell cycle proteins for degradation by the 26S proteasome. The APC/C is a large complex of 11–13 subunit proteins, including a cullin (Apc2) and RING (Apc11) subunit much like SCF. Other parts of the APC/C have unknown functions but are highly conserved.
The spindle checkpoint, also known as the metaphase-to-anaphase transition, the spindle assembly checkpoint (SAC), the metaphase checkpoint, or the mitotic checkpoint, is a cell cycle checkpoint during metaphase of mitosis or meiosis that prevents the separation of the duplicated chromosomes (anaphase) until each chromosome is properly attached to the spindle. To achieve proper segregation, the two kinetochores on the sister chromatids must be attached to opposite spindle poles. Only this pattern of attachment will ensure that each daughter cell receives one copy of the chromosome. The defining biochemical feature of this checkpoint is the stimulation of the anaphase-promoting complex by M-phase cyclin-CDK complexes, which in turn causes the proteolytic destruction of cyclins and proteins that hold the sister chromatids together.
Mad2 is an essential spindle checkpoint protein. The spindle checkpoint system is a regulatory system that restrains progression through the metaphase-to-anaphase transition. The Mad2 gene was first identified in the yeast S. cerevisiae in a screen for genes which when mutated would confer sensitivity to microtubule poisons. The human orthologues of Mad2 were first cloned in a search for human cDNAs that would rescue the microtubule poison-sensitivity of a yeast strain in which a kinetochore binding protein was missing. The protein was shown to be present at unattached kinetochores and antibody inhibition studies demonstrated it was essential to execute a block in the metaphase-to-anaphase transition in response to the microtubule poison nocodazole. Subsequent cloning of the Xenopus laevis orthologue, facilitated by the sharing of the human sequence, allowed for the characterization of the mitotic checkpoint in egg extracts.
The cell division cycle protein 20 homolog is an essential regulator of cell division that is encoded by the CDC20 gene in humans. To the best of current knowledge its most important function is to activate the anaphase promoting complex (APC/C), a large 11-13 subunit complex that initiates chromatid separation and entrance into anaphase. The APC/CCdc20 protein complex has two main downstream targets. Firstly, it targets securin for destruction, enabling the eventual destruction of cohesin and thus sister chromatid separation. It also targets S and M-phase (S/M) cyclins for destruction, which inactivates S/M cyclin-dependent kinases (Cdks) and allows the cell to exit from mitosis. A closely related protein, Cdc20homologue-1 (Cdh1) plays a complementary role in the cell cycle.
Mitotic spindle assembly checkpoint protein MAD2A is a protein that in humans is encoded by the MAD2L1 gene.
F-box only protein 5 is a protein that in humans is encoded by the FBXO5 gene.
Fizzy-related protein homolog, also known as hCDH1, is a protein that in humans is encoded by the FZR1 gene.
Cell division cycle protein 16 homolog is a protein that in humans is encoded by the CDC16 gene.
Cell division cycle 23 homolog , also known as CDC23, is a protein that, in humans, is encoded by the CDC23 gene.
Mitotic checkpoint protein BUB3 is a protein that in humans is encoded by the BUB3 gene.
Anaphase-promoting complex subunit 1 is an enzyme that in humans is encoded by the ANAPC1 gene.
Anaphase-promoting complex subunit 2 is an enzyme that in humans is encoded by the ANAPC2 gene.
Anaphase-promoting complex subunit 5 is an enzyme that in humans is encoded by the ANAPC5 gene.
Anaphase-promoting complex subunit 7 is an enzyme that in humans is encoded by the ANAPC7 gene. Multiple transcript variants encoding different isoforms have been found for this gene.
Anaphase-promoting complex subunit 10 is an enzyme that in humans is encoded by the ANAPC10 gene.
Anaphase-promoting complex subunit 4 is an enzyme that in humans is encoded by the ANAPC4 gene.
Anaphase-promoting complex subunit 11 is an enzyme that in humans is encoded by the ANAPC11 gene.
Cdh1 is one of the substrate adaptor proteins of the anaphase-promoting complex (APC) in the budding yeast Saccharomyces cerevisiae. Functioning as an activator of the APC/C, Cdh1 regulates the activity and substrate specificity of this ubiquitin E3-ligase. The human homolog is encoded by the FZR1 gene, which is not to be confused with the CDH1 gene.
Mitotic exit is an important transition point that signifies the end of mitosis and the onset of new G1 phase for a cell, and the cell needs to rely on specific control mechanisms to ensure that once it exits mitosis, it never returns to mitosis until it has gone through G1, S, and G2 phases and passed all the necessary checkpoints. Many factors including cyclins, cyclin-dependent kinases (CDKs), ubiquitin ligases, inhibitors of cyclin-dependent kinases, and reversible phosphorylations regulate mitotic exit to ensure that cell cycle events occur in correct order with fewest errors. The end of mitosis is characterized by spindle breakdown, shortened kinetochore microtubules, and pronounced outgrowth of astral (non-kinetochore) microtubules. For a normal eukaryotic cell, mitotic exit is irreversible.
The anaphase- promoting complex or cyclosome (APC/C) is a highly specific ubiquitin protein ligase responsible for triggering events of late mitosis. In early mitosis, Cdc20 levels rise and APC/C binds to form active APC/CCdc20. This then leads to the destruction of mitotic cyclins, securin, and other proteins to trigger chromosome separation in anaphase. In early anaphase, Cdk1 is inactivated, leading to the activation of Cdh1, the other activator subunit of APC/C. This then triggers the degradation of Cdc20 and leads to the activation of APC/CCdh1 through G1 to suppress S- phase cyclin-Cdk activity. At the end of G1, APC/CCdh1 is inactivated and S- phase and mitotic cyclins gets reaccumulate as the cell progresses to S phase.
