The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels
AffiliationCell Signalling Group, Cancer Research UK Manchester Institute, The University of Manchester, Alderley Park, Macclesfield SK10 4TG, UK
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AbstractCentriole duplication is tightly controlled to maintain correct centriole number through the cell cycle. Key to this is the regulated degradation of PLK4, the master regulator of centriole duplication. Here we show that the Rac1 guanine nucleotide exchange factor (GEF) Tiam1 localises to centrosomes during S-phase, where it is required for maintenance of normal centriole number. Depletion of Tiam1 leads to an increase in centrosomal PLK4 and centriole overduplication, whereas overexpression of Tiam1 can restrict centriole overduplication. Ultimately Tiam1 depletion leads to lagging chromosomes at anaphase and aneuploidy, potential drivers of malignant progression. The effects of Tiam1 depletion on centrosomal PLK4 levels and centriole overduplication can be rescued by re-expression of both wild-type Tiam1 and catalytically inactive (GEF*) Tiam1, but not by Tiam1 mutants unable to bind to the F-box protein βTRCP, implying that Tiam1 regulates PLK4 levels through promoting βTRCP-mediated degradation independently of Rac1 activation.
CitationPorter AP, Reed H, White GRM, Ogg EL, Whalley HJ, Malliri A. The RAC1 activator Tiam1 regulates centriole duplication through controlling PLK4 levels. J Cell Sci. 2021.
JournalJournal of Cell Science
- Plk4 trans-autophosphorylation regulates centriole number by controlling betaTrCP-mediated degradation.
- Authors: Guderian G, Westendorf J, Uldschmid A, Nigg EA
- Issue date: 2010 Jul 1
- Cep78 is a new centriolar protein involved in Plk4-induced centriole overduplication.
- Authors: Brunk K, Zhu M, Bärenz F, Kratz AS, Haselmann-Weiss U, Antony C, Hoffmann I
- Issue date: 2016 Jul 15
- Centriole Overduplication is the Predominant Mechanism Leading to Centrosome Amplification in Melanoma.
- Authors: Denu RA, Shabbir M, Nihal M, Singh CK, Longley BJ, Burkard ME, Ahmad N
- Issue date: 2018 Mar
- GCP6 is a substrate of Plk4 and required for centriole duplication.
- Authors: Bahtz R, Seidler J, Arnold M, Haselmann-Weiss U, Antony C, Lehmann WD, Hoffmann I
- Issue date: 2012 Jan 15
- CDK11(p58) is required for centriole duplication and Plk4 recruitment to mitotic centrosomes.
- Authors: Franck N, Montembault E, Romé P, Pascal A, Cremet JY, Giet R
- Issue date: 2011 Jan 31