| Structural highlights
Disease
[CE152_HUMAN] Seckel syndrome;Autosomal recessive primary microcephaly. The disease is caused by mutations affecting the gene represented in this entry. The disease is caused by mutations affecting the gene represented in this entry.
Function
[PLK4_HUMAN] Serine/threonine-protein kinase that plays a central role in centriole duplication. Able to trigger procentriole formation on the surface of the parental centriole cylinder, leading to the recruitment of centriole biogenesis proteins such as SASS6, CENPJ/CPAP, CCP110, CEP135 and gamma-tubulin. When overexpressed, it is able to induce centrosome amplification through the simultaneous generation of multiple procentrioles adjoining each parental centriole during S phase. Phosphorylates 'Ser-151' of FBXW5 during the G1/S transition, leading to inhibit FBXW5 ability to ubiquitinate SASS6. Its central role in centriole replication suggests a possible role in tumorigenesis, centrosome aberrations being frequently observed in tumors. Also involved in trophoblast differentiation by phosphorylating HAND1, leading to disrupt the interaction between HAND1 and MDFIC and activate HAND1. Phosphorylates CDC25C and CHEK2.[1] [2] [3] [4] [5] [6] [CE152_HUMAN] Necessary for centrosome duplication. Acts as a molecular scaffold facilitating the interaction of PLK4 and CENPJ, 2 molecules involved in centriole formation. Also plays a key role in deuterosome-mediated centriole amplification in multiciliated that can generate more than 100 centrioles. Overexpression of CEP152 can drive amplification of centrioles.[7] [8] [9]
Publication Abstract from PubMed
Polo-like kinase 4 (Plk4) is a key regulator of centriole duplication, an event critical for the maintenance of genomic integrity. We show that Plk4 relocalizes from the inner Cep192 ring to the outer Cep152 ring as newly recruited Cep152 assembles around the Cep192-encircled daughter centriole. Crystal-structure analyses revealed that Cep192- and Cep152-derived peptides bind the cryptic polo box (CPB) of Plk4 in opposite orientations and in a mutually exclusive manner. The Cep152 peptide bound to the CPB markedly better than did the Cep192 peptide and effectively 'snatched' the CPB away from a preformed CPB-Cep192 peptide complex. A cancer-associated Cep152 mutation impairing the Plk4 interaction induced defects in procentriole assembly and chromosome segregation. Thus, Plk4 is intricately regulated in time and space through ordered interactions with two distinct scaffolds, Cep192 and Cep152, and a failure in this process may lead to human cancer.
Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis.,Park SY, Park JE, Kim TS, Kim JH, Kwak MJ, Ku B, Tian L, Murugan RN, Ahn M, Komiya S, Hojo H, Kim NH, Kim BY, Bang JK, Erikson RL, Lee KW, Kim SJ, Oh BH, Yang W, Lee KS Nat Struct Mol Biol. 2014 Jun 29. doi: 10.1038/nsmb.2846. PMID:24997597[10]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bettencourt-Dias M, Rodrigues-Martins A, Carpenter L, Riparbelli M, Lehmann L, Gatt MK, Carmo N, Balloux F, Callaini G, Glover DM. SAK/PLK4 is required for centriole duplication and flagella development. Curr Biol. 2005 Dec 20;15(24):2199-207. Epub 2005 Dec 1. PMID:16326102 doi:http://dx.doi.org/10.1016/j.cub.2005.11.042
- ↑ Habedanck R, Stierhof YD, Wilkinson CJ, Nigg EA. The Polo kinase Plk4 functions in centriole duplication. Nat Cell Biol. 2005 Nov;7(11):1140-6. PMID:16244668 doi:http://dx.doi.org/10.1038/ncb1320
- ↑ Kleylein-Sohn J, Westendorf J, Le Clech M, Habedanck R, Stierhof YD, Nigg EA. Plk4-induced centriole biogenesis in human cells. Dev Cell. 2007 Aug;13(2):190-202. PMID:17681131 doi:http://dx.doi.org/10.1016/j.devcel.2007.07.002
- ↑ Bonni S, Ganuelas ML, Petrinac S, Hudson JW. Human Plk4 phosphorylates Cdc25C. Cell Cycle. 2008 Feb 15;7(4):545-7. Epub 2007 Nov 25. PMID:18239451
- ↑ Petrinac S, Ganuelas ML, Bonni S, Nantais J, Hudson JW. Polo-like kinase 4 phosphorylates Chk2. Cell Cycle. 2009 Jan 15;8(2):327-9. PMID:19164942
- ↑ Puklowski A, Homsi Y, Keller D, May M, Chauhan S, Kossatz U, Grunwald V, Kubicka S, Pich A, Manns MP, Hoffmann I, Gonczy P, Malek NP. The SCF-FBXW5 E3-ubiquitin ligase is regulated by PLK4 and targets HsSAS-6 to control centrosome duplication. Nat Cell Biol. 2011 Jul 3;13(8):1004-9. doi: 10.1038/ncb2282. PMID:21725316 doi:http://dx.doi.org/10.1038/ncb2282
- ↑ Cizmecioglu O, Arnold M, Bahtz R, Settele F, Ehret L, Haselmann-Weiss U, Antony C, Hoffmann I. Cep152 acts as a scaffold for recruitment of Plk4 and CPAP to the centrosome. J Cell Biol. 2010 Nov 15;191(4):731-9. doi: 10.1083/jcb.201007107. Epub 2010 Nov , 8. PMID:21059844 doi:http://dx.doi.org/10.1083/jcb.201007107
- ↑ Dzhindzhev NS, Yu QD, Weiskopf K, Tzolovsky G, Cunha-Ferreira I, Riparbelli M, Rodrigues-Martins A, Bettencourt-Dias M, Callaini G, Glover DM. Asterless is a scaffold for the onset of centriole assembly. Nature. 2010 Oct 7;467(7316):714-8. doi: 10.1038/nature09445. Epub 2010 Sep 19. PMID:20852615 doi:http://dx.doi.org/10.1038/nature09445
- ↑ Kalay E, Yigit G, Aslan Y, Brown KE, Pohl E, Bicknell LS, Kayserili H, Li Y, Tuysuz B, Nurnberg G, Kiess W, Koegl M, Baessmann I, Buruk K, Toraman B, Kayipmaz S, Kul S, Ikbal M, Turner DJ, Taylor MS, Aerts J, Scott C, Milstein K, Dollfus H, Wieczorek D, Brunner HG, Hurles M, Jackson AP, Rauch A, Nurnberg P, Karaguzel A, Wollnik B. CEP152 is a genome maintenance protein disrupted in Seckel syndrome. Nat Genet. 2011 Jan;43(1):23-6. doi: 10.1038/ng.725. Epub 2010 Dec 5. PMID:21131973 doi:http://dx.doi.org/10.1038/ng.725
- ↑ Park SY, Park JE, Kim TS, Kim JH, Kwak MJ, Ku B, Tian L, Murugan RN, Ahn M, Komiya S, Hojo H, Kim NH, Kim BY, Bang JK, Erikson RL, Lee KW, Kim SJ, Oh BH, Yang W, Lee KS. Molecular basis for unidirectional scaffold switching of human Plk4 in centriole biogenesis. Nat Struct Mol Biol. 2014 Jun 29. doi: 10.1038/nsmb.2846. PMID:24997597 doi:http://dx.doi.org/10.1038/nsmb.2846
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