Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number

@article{CunhaFerreira2013RegulationOA,
  title={Regulation of Autophosphorylation Controls PLK4 Self-Destruction and Centriole Number},
  author={In{\^e}s Cunha-Ferreira and Ines Bento and Ana Pimenta-Marques and Swadhin Chandra Jana and Mariana Lince-Faria and Paulo Duarte and Joana Borrego-Pinto and Samuel Gilberto and Tiago Amado and Daniela A. Brito and Ana Rodrigues-Martins and Janusz Debski and Nikola Dzhindzhev and M{\'o}nica Bettencourt-Dias},
  journal={Current Biology},
  year={2013},
  volume={23},
  pages={2245-2254}
}

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References

SHOWING 1-10 OF 41 REFERENCES

Plk4 trans-autophosphorylation regulates centriole number by controlling βTrCP-mediated degradation

TLDR
It is shown that human Plk4 is subject to βTrCP-dependent proteasomal degradation, indicating that this pathway is conserved from Drosophila to human, and it is found that stable overexpression of kinase-dead PlK4 leads to centriole overduplication.

Polo-like kinase 4: the odd one out of the family

TLDR
Past and present data discussing the regulation and functions of PLK4 are overviewed, certain that additional regulatory mechanisms exist to safeguard the fidelity of centriole duplication.

The Polo kinase Plk4 functions in centriole duplication

TLDR
It is identified that Plk4 is required — in cooperation with Cdk2, CP110 and Hs-SAS6 — for the precise reproduction of centrosomes during the cell cycle and this findings provide an attractive explanation for the crucial function of PlK4 in cell proliferation.

Hierarchical order of phosphorylation events commits Cdc25A to Beta-TrCP-dependent degradation

TLDR
It is shown that phosphorylation at Ser 82 within the DSG motif anchors Cdc25A to βTrCP and that Chk1-dependent phosphorylated at Ser 76 affects this interaction as well as βTr CP-dependent degradation.

Deregulated proteolysis by the F-box proteins SKP2 and β-TrCP: tipping the scales of cancer

TLDR
The functionality and biology of the F-box proteins, SKP2 (S-phase kinase-associated protein 2) and β-TrCP (β-transducin repeat-containing protein), are explored, which are emerging as important players in cancer biogenesis owing to the deregulated proteolysis of their substrates.

Autophosphorylation of Polo-like Kinase 4 and Its Role in Centriole Duplication

TLDR
It is shown that PLK4 is active beyond the initiation of centriole duplication with the abundance of active kinase increasing to a peak in mitosis and that active PLK 4 is restricted to the centrosome.

Casein Kinase 1 Functions as both Penultimate and Ultimate Kinase in Regulating Cdc25A Destruction

TLDR
It is reported that casein kinase 1 α (CK1α) phosphorylates CDC25A on both S79 and S82 in a hierarchical manner requiring prior phosphorylation of S76 by Chk1 or GSK-3β, which facilitates β-TrCP binding and ubiquitin-mediated proteolysis of Cdc25A throughout interphase and after exposure to genotoxic stress.