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

@article{Guderian2010Plk4TR,
  title={Plk4 trans-autophosphorylation regulates centriole number by controlling $\beta$TrCP-mediated degradation},
  author={Gernot Guderian and Jens Westendorf and Andreas Uldschmid and Erich A. Nigg},
  journal={Journal of Cell Science},
  year={2010},
  volume={123},
  pages={2163 - 2169}
}
Centrioles are the main constituents of the mammalian centrosome and act as basal bodies for ciliogenesis. Centrosomes organize the cytoplasmic microtubule network during interphase and the mitotic spindle during mitosis, and aberrations in centrosome number have been implicated in chromosomal instability and tumor formation. The centriolar protein Polo-like kinase 4 (Plk4) is a key regulator of centriole biogenesis and is crucial for maintaining constant centriole number, but the mechanisms… 

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Control of centriole numbers by Plk4 autophosphorylation and βTrCP-mediated degradation

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References

SHOWING 1-10 OF 47 REFERENCES

Cullin 1 functions as a centrosomal suppressor of centriole multiplication by regulating polo-like kinase 4 protein levels.

TLDR
The results suggest that CUL1 may function as a tumor suppressor by regulating PLK4 protein levels and thereby restraining excessive daughter centriole formation at maternal centrioles.

Plk1 regulates mitotic Aurora A function through βTrCP-dependent degradation of hBora

TLDR
It is shown that the functions of these kinases during early mitosis are coordinated through Bora, a partner of Aurora A first identified in Drosophila, and suggests that Plk1 controls Aurora A localization and function by regulating cellular levels of hBora.

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.

Control of Meiotic and Mitotic Progression by the F Box Protein β-Trcp1 In Vivo

Control of meiotic and mitotic progression by the F box protein beta-Trcp1 in vivo.

TLDR
Beta-Trcp1 regulates the timely order of meiotic and mitotic events and it is demonstrated that Emi1 is a bona fide substrate of beta-TrCP1.

Sequential Protein Recruitment in C. elegans Centriole Formation

SAS-4 is recruited to a dynamic structure in newly forming centrioles that is stabilized by the γ-tubulin–mediated addition of centriolar microtubules

TLDR
It is shown that SAS-4 and SAS-6 are coordinately recruited to the site of new centriole assembly and reach their maximum levels during S phase, which indicates that γ-tubulin in the PCM stabilizes the nascent daughter centrioles by promoting microtubule addition to its outer wall.