SAK

Summary

Gene Symbol: SAK
Description: Sak kinase
Alias: CG7186, DmSAK, Dmel\CG7186, PLK4, Plk4, SAK/PLK, SAK/PLK4, Sak, Sak/Plk4, plk4, sak, Sak kinase, CG7186-PA, Polo-like kinase 4, SAK-PA
Species: fruit fly
Products:     SAK

Top Publications

  1. Rodrigues Martins A, Riparbelli M, Callaini G, Glover D, Bettencourt Dias M. Revisiting the role of the mother centriole in centriole biogenesis. Science. 2007;316:1046-50 pubmed
    ..SAK, also called PLK4 (SAK/PLK4), a kinase implicated in tumor development, is an upstream regulator of canonical biogenesis necessary ..
  2. Peel N, Stevens N, Basto R, Raff J. Overexpressing centriole-replication proteins in vivo induces centriole overduplication and de novo formation. Curr Biol. 2007;17:834-43 pubmed
    ..Here, we investigate the effects of overexpressing the three proteins known to be required for centriole replication in Drosophila-DSas-6, DSas-4, and Sak.
  3. Cunha Ferreira I, Bento I, Pimenta Marques A, Jana S, Lince Faria M, Duarte P, et al. Regulation of autophosphorylation controls PLK4 self-destruction and centriole number. Curr Biol. 2013;23:2245-2254 pubmed publisher
    Polo-like kinase 4 (PLK4) is a major player in centriole biogenesis: in its absence centrioles fail to form, while in excess leads to centriole amplification...
  4. Fu J, Glover D. Structured illumination of the interface between centriole and peri-centriolar material. Open Biol. 2012;2:120104 pubmed publisher
    ..Sas-4, Spd-2 and Polo kinase; and an outer layer comprising Pericentrin-like protein (Dplp), Asterless (Asl) and Plk4 kinase...
  5. Blachon S, Cai X, Roberts K, Yang K, Polyanovsky A, Church A, et al. A proximal centriole-like structure is present in Drosophila spermatids and can serve as a model to study centriole duplication. Genetics. 2009;182:133-44 pubmed publisher
    ..Second, the centriolar proteins SAS-6, Ana1, and Bld10p/Cep135 are in the PCL. Third, PCL formation depends on SAK/PLK4 and SAS-6...
  6. Stevens N, Roque H, Raff J. DSas-6 and Ana2 coassemble into tubules to promote centriole duplication and engagement. Dev Cell. 2010;19:913-9 pubmed publisher
    ..Centriole duplication relies on a few conserved proteins (ZYG-1/Sak/Plk4, SAS-6, SAS-5/Ana2, and SAS-4), and is often initiated by the formation of an inner "cartwheel" structure...
  7. Castellanos E, Dominguez P, Gonzalez C. Centrosome dysfunction in Drosophila neural stem cells causes tumors that are not due to genome instability. Curr Biol. 2008;18:1209-14 pubmed publisher
    ..We propose that such tumors might be caused by impaired asymmetric division of neural stem cells [4]. These results show that centrosome loss, far from being innocuous, is a potentially dangerous condition in flies...
  8. Rogers G, Rusan N, Roberts D, Peifer M, Rogers S. The SCF Slimb ubiquitin ligase regulates Plk4/Sak levels to block centriole reduplication. J Cell Biol. 2009;184:225-39 pubmed publisher
    ..in complex with the F-box protein Slimb mediates proteolytic degradation of the centrosomal regulatory kinase Plk4. We identified SCF(Slimb) as a regulator of centriole duplication via an RNA interference (RNAi) screen of Cullin-..
  9. Stevens N, Dobbelaere J, Brunk K, Franz A, Raff J. Drosophila Ana2 is a conserved centriole duplication factor. J Cell Biol. 2010;188:313-23 pubmed publisher
    ..In Drosophila melanogaster and humans, Sak/Plk4, DSas-6/hSas-6, and DSas-4/CPAP-orthologues of ZYG-1, SAS-6, and SAS-4, respectively-are required for centriole ..

More Information

Publications43

  1. Carvalho Santos Z, Machado P, Branco P, Tavares Cadete F, Rodrigues Martins A, Pereira Leal J, et al. Stepwise evolution of the centriole-assembly pathway. J Cell Sci. 2010;123:1414-26 pubmed publisher
    ..Unexpectedly, other players (SAK/PLK4, SPD2/CEP192 and CP110) emerged in a taxon-specific manner...
  2. Dzhindzhev N, Yu Q, Weiskopf K, Tzolovsky G, Cunha Ferreira I, Riparbelli M, et al. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010;467:714-8 pubmed publisher
    ..Centriole assembly and duplication is controlled by Polo-like-kinase 4 (Plk4): these processes fail if Plk4 is downregulated and are promoted by Plk4 overexpression...
  3. Brownlee C, Klebba J, Buster D, Rogers G. The Protein Phosphatase 2A regulatory subunit Twins stabilizes Plk4 to induce centriole amplification. J Cell Biol. 2011;195:231-43 pubmed publisher
    ..b>Plk4 (Polo-like kinase 4) activity initiates centriole duplication and is regulated by ubiquitin-mediated proteolysis...
  4. Bettencourt Dias M, Rodrigues Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt M, et al. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005;15:2199-207 pubmed
    SAK/PLK4 is a distinct member of the polo-like kinase family. SAK-/- mice die during embryogenesis, whereas SAK+/- mice develop liver and lung tumors and SAK+/- MEFs show mitotic abnormalities...
  5. Gopalakrishnan J, Mennella V, Blachon S, Zhai B, Smith A, Megraw T, et al. Sas-4 provides a scaffold for cytoplasmic complexes and tethers them in a centrosome. Nat Commun. 2011;2:359 pubmed publisher
    ..In summary, PCM assembly begins in the cytosol where Sas-4 provides a scaffold for pre-assembled cytoplasmic complexes before tethering of the complexes in a centrosome. ..
  6. Stevens N, Dobbelaere J, Wainman A, Gergely F, Raff J. Ana3 is a conserved protein required for the structural integrity of centrioles and basal bodies. J Cell Biol. 2009;187:355-63 pubmed publisher
    ..Thus, Ana3 defines a conserved family of centriolar proteins and plays an important part in ensuring the structural integrity of centrioles and basal bodies. ..
  7. Cunha Ferreira I, Rodrigues Martins A, Bento I, Riparbelli M, Zhang W, Laue E, et al. The SCF/Slimb ubiquitin ligase limits centrosome amplification through degradation of SAK/PLK4. Curr Biol. 2009;19:43-9 pubmed publisher
    ..Centriole formation is triggered and dependent on a conserved kinase, SAK/PLK4. Downregulation and overexpression of SAK/PLK4 is associated with cancer in humans, mice, and flies...
  8. Basto R, Brunk K, Vinadogrova T, Peel N, Franz A, Khodjakov A, et al. Centrosome amplification can initiate tumorigenesis in flies. Cell. 2008;133:1032-42 pubmed publisher
    ..Thus, centrosome amplification can initiate tumorigenesis in flies. ..
  9. Baumbach J, Levesque M, Raff J. Centrosome loss or amplification does not dramatically perturb global gene expression in Drosophila. Biol Open. 2012;1:983-93 pubmed publisher
    ..These observations indicate that centrosome defects can predispose fly brain cells to form tumours without, at least initially, dramatically altering their physiology. ..
  10. Perkins L, Holderbaum L, Tao R, Hu Y, Sopko R, McCall K, et al. The Transgenic RNAi Project at Harvard Medical School: Resources and Validation. Genetics. 2015;201:843-52 pubmed publisher
    ..flyrnai.org/RSVP.html), and stocks are available from three stock centers, the Bloomington Drosophila Stock Center (United States), National Institute of Genetics (Japan), and TsingHua Fly Center (China). ..
  11. Li S, Wang C, Sandanaraj E, Aw S, Koe C, Wong J, et al. The SCFSlimb E3 ligase complex regulates asymmetric division to inhibit neuroblast overgrowth. EMBO Rep. 2014;15:165-74 pubmed publisher
    ..Slimb associates with Akt in a protein complex, and SCF(S)(limb) acts through SAK and Akt to inhibit neuroblast overgrowth...
  12. Rodrigues Martins A, Riparbelli M, Callaini G, Glover D, Bettencourt Dias M. From centriole biogenesis to cellular function: centrioles are essential for cell division at critical developmental stages. Cell Cycle. 2008;7:11-6 pubmed
    ..demonstrating a molecular pathway that operates in both de novo and canonical centriole biogenesis involving SAK/PLK4, SAS-6 and SAS-4...
  13. Goodwin S, Vale R. Patronin regulates the microtubule network by protecting microtubule minus ends. Cell. 2010;143:263-74 pubmed publisher
    ..We propose that Patronin caps and stabilizes microtubule minus ends, an activity that serves a critical role in the organization of the microtubule cytoskeleton. ..
  14. Skwarek L, Windler S, de Vreede G, Rogers G, Bilder D. The F-box protein Slmb restricts the activity of aPKC to polarize epithelial cells. Development. 2014;141:2978-83 pubmed publisher
    ..The involvement of the Slmb E3 ligase in epithelial polarity, specifically limiting Par complex activity to distinguish the basolateral domain, points to parallels with polarization of the C. elegans zygote. ..
  15. Franz A, Roque H, Saurya S, Dobbelaere J, Raff J. CP110 exhibits novel regulatory activities during centriole assembly in Drosophila. J Cell Biol. 2013;203:785-99 pubmed publisher
    ..Finally, and unexpectedly, CP110 suppresses centriole overduplication induced by the overexpression of centriole duplication proteins. These studies identify novel and surprising functions for CP110 in vivo in flies. ..
  16. Li W, Miki T, Watanabe T, Kakeno M, Sugiyama I, Kaibuchi K, et al. EB1 promotes microtubule dynamics by recruiting Sentin in Drosophila cells. J Cell Biol. 2011;193:973-83 pubmed publisher
    ..These results indicate that EB1 promotes dynamic microtubule behavior by recruiting the cargo protein Sentin and possibly also a microtubule polymerase to the microtubule tip. ..
  17. Sabino D, Brown N, Basto R. Drosophila Ajuba is not an Aurora-A activator but is required to maintain Aurora-A at the centrosome. J Cell Sci. 2011;124:1156-66 pubmed publisher
    ..On the basis of our studies in Drosophila neuroblasts, we propose that a key function of Ajuba, in these cells, is to maintain active Aur-A at the centrosome during mitosis. ..
  18. Gogendeau D, Siudeja K, Gambarotto D, Pennetier C, Bardin A, Basto R. Aneuploidy causes premature differentiation of neural and intestinal stem cells. Nat Commun. 2015;6:8894 pubmed publisher
    ..Our work highlights a neural and intestine stem cell-specific response to aneuploidy, which prevents their proliferation and expansion. ..
  19. Galletta B, Fagerstrom C, Schoborg T, McLamarrah T, Ryniawec J, Buster D, et al. A centrosome interactome provides insight into organelle assembly and reveals a non-duplication role for Plk4. Nat Commun. 2016;7:12476 pubmed publisher
    ..Finally, we identified a novel role for Plk4, the master regulator of centriole duplication...
  20. Klebba J, Galletta B, Nye J, Plevock K, Buster D, Hollingsworth N, et al. Two Polo-like kinase 4 binding domains in Asterless perform distinct roles in regulating kinase stability. J Cell Biol. 2015;208:401-14 pubmed publisher
    b>Plk4 (Polo-like kinase 4) and its binding partner Asterless (Asl) are essential, conserved centriole assembly factors that induce centriole amplification when overexpressed...
  21. Gottardo M, Callaini G, Riparbelli M. Klp10A modulates the localization of centriole-associated proteins during Drosophila male gametogenesis. Cell Cycle. 2016;15:3432-3441 pubmed publisher
    ..In the absence of Klp10A the distribution of Drosophila pericentrin-like protein (Dplp), Sas-4 and Sak/Plk4 that are restricted in control testes to the proximal end of the centriole increase along the centriole length...
  22. Klebba J, Buster D, McLamarrah T, Rusan N, Rogers G. Autoinhibition and relief mechanism for Polo-like kinase 4. Proc Natl Acad Sci U S A. 2015;112:E657-66 pubmed publisher
    Polo-like kinase 4 (Plk4) is a master regulator of centriole duplication, and its hyperactivity induces centriole amplification...
  23. Schoenfelder K, Montague R, Paramore S, Lennox A, Mahowald A, Fox D. Indispensable pre-mitotic endocycles promote aneuploidy in the Drosophila rectum. Development. 2014;141:3551-60 pubmed publisher
    ..Together, our results demonstrate that pre-mitotic endocycles can enable specific organ construction and are a mechanism that promotes highly tolerated aneuploidy. ..
  24. Shimanovskaya E, Viscardi V, Lesigang J, Lettman M, Qiao R, Svergun D, et al. Structure of the C. elegans ZYG-1 cryptic polo box suggests a conserved mechanism for centriolar docking of Plk4 kinases. Structure. 2014;22:1090-1104 pubmed publisher
    b>Plk4 family kinases control centriole assembly. Plk4s target mother centrioles through an interaction between their cryptic polo box (CPB) and acidic regions in the centriolar receptors SPD-2/Cep192 and/or Asterless/Cep152...
  25. Klebba J, Buster D, Nguyen A, Swatkoski S, Gucek M, Rusan N, et al. Polo-like kinase 4 autodestructs by generating its Slimb-binding phosphodegron. Curr Biol. 2013;23:2255-2261 pubmed publisher
    Polo-like kinase 4 (Plk4) is a conserved master regulator of centriole assembly. Previously, we found that Drosophila Plk4 protein levels are actively suppressed during interphase...
  26. Galletta B, Jacobs K, Fagerstrom C, Rusan N. Asterless is required for centriole length control and sperm development. J Cell Biol. 2016;213:435-50 pubmed publisher
    ..Insights into the role of Asl/Cep152 beyond centriole duplication could help shed light on how Cep152 mutations lead to the development of microcephaly. ..
  27. Przewloka M, Venkei Z, Bolanos Garcia V, Debski J, Dadlez M, Glover D. CENP-C is a structural platform for kinetochore assembly. Curr Biol. 2011;21:399-405 pubmed publisher
    ..part was sufficient to recruit KMN proteins, we targeted it to the centrosome by fusing it to a domain of Plk4 kinase...
  28. Dzhindzhev N, Tzolovsky G, Lipinszki Z, Schneider S, Lattao R, Fu J, et al. Plk4 phosphorylates Ana2 to trigger Sas6 recruitment and procentriole formation. Curr Biol. 2014;24:2526-32 pubmed publisher
    ..elegans ZYG-1 or its Polo-like kinase 4 (Plk4) counterpart in other organisms...
  29. Moutinho Pereira S, Debec A, Maiato H. Microtubule cytoskeleton remodeling by acentriolar microtubule-organizing centers at the entry and exit from mitosis in Drosophila somatic cells. Mol Biol Cell. 2009;20:2796-808 pubmed publisher
    ..Our data reveal a new form of cell cycle-regulated MTOCs that contribute for MT cytoskeleton remodeling during mitotic spindle assembly/disassembly in animal somatic cells, independently of centrioles. ..
  30. Sabino D, Gogendeau D, Gambarotto D, Nano M, Pennetier C, Dingli F, et al. Moesin is a major regulator of centrosome behavior in epithelial cells with extra centrosomes. Curr Biol. 2015;25:879-89 pubmed publisher
    ..This study provides a mechanistic explanation for the increased aneuploidy and transformation potential primed by centrosome amplification in epithelial tissues. ..
  31. Khire A, Vizuet A, Davila E, Avidor Reiss T. Asterless Reduction during Spermiogenesis Is Regulated by Plk4 and Is Essential for Zygote Development in Drosophila. Curr Biol. 2015;25:2956-63 pubmed publisher
    ..Asl reduction is regulated through a subset of its domains by the master regulator of centriole duplication Plk4 and by the ubiquitin ligase that targets Plk4 for degradation: Slimb...
  32. Carvajal Gonzalez J, Roman A, Mlodzik M. Positioning of centrioles is a conserved readout of Frizzled planar cell polarity signalling. Nat Commun. 2016;7:11135 pubmed publisher
    ..Together with vertebrate data, these results suggest a unifying model of centriole/cilia positioning as a common downstream effect of PCP signalling from flies to mammals. ..
  33. Martins A, Machado P, Callaini G, Bettencourt Dias M. Microscopy methods for the study of centriole biogenesis and function in Drosophila. Methods Cell Biol. 2010;97:223-42 pubmed publisher
    ..These methods have been widely used to study centriole assembly and its function as a centrosome organizer during mitotic and meiotic cell divisions and as an axoneme nucleator in the formation of flagella...
  34. Lopes C, Jana S, Cunha Ferreira I, Zitouni S, Bento I, Duarte P, et al. PLK4 trans-Autoactivation Controls Centriole Biogenesis in Space. Dev Cell. 2015;35:222-35 pubmed publisher
    ..Here, we show that trans-autoactivation of Polo-like kinase 4 (PLK4), the trigger of centriole biogenesis, is a critical event in the spatial control of that process...