STIL binding to Polo-box 3 of PLK4 regulates centriole duplication

Arquint, Christian; Gabryjonczyk, Anna-Maria; Imseng, Stefan; Böhm, Raphael; Sauer, Evelyn; Hiller, Sebastian; Nigg, Erich A.; Maier, Timm

doi:10.7554/elife.07888

Cited by 121 publications

(199 citation statements)

References 92 publications

(200 reference statements)

Supporting

Mentioning

171

Contrasting

Unclassified

Order By: Relevance

“…1A). The recently identified Plk4 substrate STIL also binds to regions of Plk4 that are situated outside of the Plk4 polo-box domain (Kratz et al, 2015;Arquint et al, 2015), suggesting different interaction platforms within Plk4. The observed interaction between Cep78 and Plk4 could further be confirmed in GST pulldown experiments using bacterially expressed GST-Cep78 to pull down Flag-Plk4 transfected in 293T cells (Fig.…”

Section: Results and Discussion Cep78 Is A Plk4-interacting Proteinmentioning

confidence: 99%

“…Few substrates of Plk4 have been described to date, including STIL (Ohta et al, 2014;Dzhindzhev et al, 2014;Kratz et al, 2015;Arquint et al, 2015;Moyer et al, 2015), GCP6 (also known as TUBGCP6) (Bahtz et al, 2012;Martin et al, 2014) and the F-box protein Fbxw5, a component of the SCF ubiquitin ligase (Puklowski et al, 2011). Cep152 and Cep192 collaborate to recruit Plk4 to centrioles (Cizmecioglu et al, 2010;Hatch et al, 2010;Dzhindzhev et al, 2010;Sonnen et al, 2013;Kim et al, 2013) in order to concentrate Plk4 at the centrioles and facilitate subsequent activation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Brunk

Zhu

Bärenz

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

Centrioles are core components of centrosomes, the major microtubule-organizing centers of animal cells, and act as basal bodies for cilia formation. Control of centriole number is therefore crucial for genome stability and embryogenesis. Centriole duplication requires the serine/threonine protein kinase Plk4. Here, we identify Cep78 as a human centrosomal protein and a new interaction partner of Plk4. Cep78 is mainly a centriolar protein that localizes to the centriolar wall. Furthermore, we find that Plk4 binds to Cep78 through its N-terminal domain but that Cep78 is not an in vitro Plk4 substrate. Cep78 colocalizes with Plk4 at centrioles and is required for Plk4-induced centriole overduplication. Interestingly, upon depletion of Cep78, newly synthesized Plk4 is not localized to centrosomes. Our results suggest that the interaction between Cep78 and the N-terminal catalytic domain of Plk4 is a new and important element in the centrosome overduplication process.

show abstract

Section: Results and Discussion Cep78 Is A Plk4-interacting Proteinmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Brunk

Zhu

Bärenz

et al. 2016

Journal of Cell Science

View full text Add to dashboard Cite

show abstract

“…Plk4 exists as a stable homodimer and low steady-state levels arise from PLK4 trans-autophosphorylation within the dimer, which triggers SCF-β-TrCP-mediated proteolytic degradation 103–107 . Upon binding to STIL, PLK4 undergoes a conformational change and is activated through trans-phosphorylation within the activation segment 28,108,109 . Activated PLK4 then phosphorylates STIL within the so-called STAN motif, triggering the centriolar recruitment of SAS-6 and cartwheel formation 26–29 (Figure 2B).…”

Section: Control Of Centriole Numbermentioning

confidence: 99%

“…One plausible view invokes a symmetry-breaking event that leads to the stochastic choice of a building site and suppression of all other potential sites (Figure 2B). In one attractive model, STIL is proposed to stabilize PLK4 at the site of procentriole assembly, allowing the remaining PLK4 within the ring to be turned over by self-catalyzed degradation 26,109 . Such a process would be controlled by both PLK4 kinase activity and counteracting phosphatases and would likely involve multiple feed-back loops, as suggested by theoretical modeling of the role of GTPases in symmetry-breaking during yeast cell polarization 114 .…”

Section: Control Of Centriole Numbermentioning

confidence: 99%

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Nigg

Holland

2018

Nat Rev Mol Cell Biol

419

546

View full text Add to dashboard Cite

Centrioles are conserved microtubule-based organelles that form the core of the centrosome and act as templates for the formation of cilia and flagella. Centrioles have important roles in most microtubule related processes, including motility, cell division and cell signaling. To coordinate these diverse cellular processes, centriole number must be tightly controlled. In cycling cells, one new centriole is formed next to each preexisting centriole in every cell cycle. Advances in imaging, proteomics, structural biology and genome editing have revealed new insights into centriole biogenesis, how centriole numbers are controlled and how alterations in these structures contribute to diseases such as cancer and neurodevelopmental disorders. Moreover, recent work has uncovered the existence of surveillance pathways that limit proliferation of cells with numerical centriole aberrations. Here we discuss recent progress in this field with a focus on signaling pathways and molecular mechanisms.

show abstract

“…Both the appendages and the PCM are critical to the function of centrioles and centrosomes as microtubule organizing centres and as signalling platforms. The topics of PCM assembly and function [60] and the centrosome as a signalling platform [61] are treated elsewhere in this volume.…”

Section: Outside the Microtubule Scaffoldmentioning

confidence: 99%

Centriole structure

Winey

O’Toole

2014

Phil. Trans. R. Soc. B

114

View full text Add to dashboard Cite

Centrioles are among the largest protein-based structures found in most cell types, measuring approximately 250 nm in diameter and approximately 500 nm long in vertebrate cells. Here, we briefly review ultrastructural observations about centrioles and associated structures. At the core of most centrioles is a microtubule scaffold formed from a radial array of nine triplet microtubules. Beyond the microtubule triplets of the centriole, we discuss the critically important cartwheel structure and the more enigmatic luminal density, both found on the inside of the centriole. Finally, we discuss the connectors between centrioles, and the distal and subdistal appendages outside of the microtubule scaffold that reflect centriole age and impart special functions to the centriole. Most of the work we review has been done with electron microscopy or electron tomography of resin-embedded samples, but we also highlight recent work performed with cryoelectron microscopy, cryotomography and subvolume averaging. Significant opportunities remain in the description of centriolar structure, both in mapping of component proteins within the structure and in determining the effect of mutations on components that contribute to the structure and function of the centriole.

show abstract

STIL binding to Polo-box 3 of PLK4 regulates centriole duplication

Cited by 121 publications

References 92 publications

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication

Once and only once: mechanisms of centriole duplication and their deregulation in disease

Centriole structure

Contact Info

Product

Resources

About