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

Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T - Elife (2015)

Bottom Line: STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region.In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding.We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Basel, Switzerland.

ABSTRACT
Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

No MeSH data available.


Related in: MedlinePlus

DOI:http://dx.doi.org/10.7554/eLife.07888.023
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fig8: DOI:http://dx.doi.org/10.7554/eLife.07888.023

Mentions: Deletion of the CC domain strongly disturbs centriolar localization, suggesting that it plays a dominant role in STIL localization via PLK4-mediated recruitment. In line with this, a clean deletion of the STAN domain does not significantly perturb centriolar localization of STIL (as also shown by Ohta et al., 2014, see Author response image 1). However, truncation of STIL at amino acid 1060 (which removes the STAN domain plus some downstream C-terminal residues), interferes with correct localization (as shown by Vulprecht et al., 2012 and confirmed in Arquint et al., 2014), whereas removal of only the C-terminal downstream residues does not perturb centriolar localization nor interfere with the ability of STIL to cause robust centriole amplification (Arquint et al., 2014).


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

Arquint C, Gabryjonczyk AM, Imseng S, Böhm R, Sauer E, Hiller S, Nigg EA, Maier T - Elife (2015)

DOI:http://dx.doi.org/10.7554/eLife.07888.023
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4530586&req=5

fig8: DOI:http://dx.doi.org/10.7554/eLife.07888.023
Mentions: Deletion of the CC domain strongly disturbs centriolar localization, suggesting that it plays a dominant role in STIL localization via PLK4-mediated recruitment. In line with this, a clean deletion of the STAN domain does not significantly perturb centriolar localization of STIL (as also shown by Ohta et al., 2014, see Author response image 1). However, truncation of STIL at amino acid 1060 (which removes the STAN domain plus some downstream C-terminal residues), interferes with correct localization (as shown by Vulprecht et al., 2012 and confirmed in Arquint et al., 2014), whereas removal of only the C-terminal downstream residues does not perturb centriolar localization nor interfere with the ability of STIL to cause robust centriole amplification (Arquint et al., 2014).

Bottom Line: STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region.In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding.We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

View Article: PubMed Central - PubMed

Affiliation: Biozentrum, University of Basel, Basel, Switzerland.

ABSTRACT
Polo-like kinases (PLK) are eukaryotic regulators of cell cycle progression, mitosis and cytokinesis; PLK4 is a master regulator of centriole duplication. Here, we demonstrate that the SCL/TAL1 interrupting locus (STIL) protein interacts via its coiled-coil region (STIL-CC) with PLK4 in vivo. STIL-CC is the first identified interaction partner of Polo-box 3 (PB3) of PLK4 and also uses a secondary interaction site in the PLK4 L1 region. Structure determination of free PLK4-PB3 and its STIL-CC complex via NMR and crystallography reveals a novel mode of Polo-box-peptide interaction mimicking coiled-coil formation. In vivo analysis of structure-guided STIL mutants reveals distinct binding modes to PLK4-PB3 and L1, as well as interplay of STIL oligomerization with PLK4 binding. We suggest that the STIL-CC/PLK4 interaction mediates PLK4 activation as well as stabilization of centriolar PLK4 and plays a key role in centriole duplication.

No MeSH data available.


Related in: MedlinePlus