Abstract
Among the multiple and intriguing roles of centrosomes in cellular functions is the ubiquitin–proteasome-mediated protein degradation. It has been shown that proteasomes are concentrated at the mammalian centrosome which led to further studies to view the centrosome as a proteolytic center (Wojcik et al. 1996; Wigley et al. 1999; reviewed in Badano et al. 2005). Proteasomal components that are concentrated around the centrosome include ubiquitin, the 20S and 19S subunits of the proteasome, as well as the E3 enzyme parkin. These proteasomal components colocalize with the centrosomal marker γ-tubulin and co-purify with γ-tubulin in the centrosomal fractions after sucrose-gradient ultracentrifugation (Wigley et al. 1999). The localization, accumulation, and concentration of proteasomal components around centrosomes appear to be microtubule independent which has been shown experimentally by inhibiting microtubule functions. When intracellular levels of misfolded proteins were experimentally increased by either proteasome inhibition with drugs such as lactacystin, or by overexpression of misfolded mutant proteins, the centrosome-associated proteasome network became expanded and proteolytic components were recruited from the cytosol without involvement of microtubules. These studies revealed a critical role of centrosomes in the organization and subcellular localization of proteasomes (Wigley et al. 1999; Fabunmi et al. 2000).
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Andersen JS, Wilkinson CJ, Mayor T, Mortensen P, Nigg EA, Mann M (2003) Proteomic characterization of the human centrosome by protein correlation profiling. Nature 426:570–574
Ansley SJ et al (2003) Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome. Nature 425:628–633
Badano JL, Teslovich TM, Katsanis N (2005) The centrosome in human genetic disease. Nat Rev Genet 6:194–207
Blacque OE et al (2004) Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport. Genes Dev 18:1630–1642
DiAntonio A, Hicke L (2004) Ubiquitin-dependent regulation of the synapse. Annu Rev Neurosci 27:223–246
Fabunmi RP, Wigley WC, Thomas PJ, DeMartin GN (2000) Activity and regulation of the centrosome-associated proteasome. J Biol Chem 275:409–413
Gauthier LR et al (2004) Huntingtin controls neurotrophic support and survival of neurons by enhancing BDNF vesicular transport along microtubules. Cell 118:127–138
Harjes P, Wanker EE (2003) The hunt for huntingtin function: interaction partners tell many different stories. Trends Biochem Sci 28:425–433
Imai Y, Soda M, Takahashi R (2000) Parkin suppresses unfolded protein stress-induced cell death through its E3 ubiquitin-protein ligase activity. J Biol Chem 275:35661–35664
Ishikawa A, Tsuji S (1996) Clinical analysis of 17 patients in 12 Japanese families with autosomal-recessive type juvenile parkinsonism. Neurology 47:160–166
Izzi L, Attisano L (2004) Regulation of the TGFβ signaling pathway by ubiquitin-mediated degradation. Oncogene 23:2071–2078
Katsanis N (2004) The oligogenic properties of Bardet–Biedl syndrome. Hum Mol Genet 13:R65–R71
Kim JC et al (2004) The Bardet–Biedl protein BBS4 targets cargo to the pericentriolar region and is required for microtubule anchoring and cell cycle progression. Nat Genet 36:462–470
Kitada T et al (1998) Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature 392:605–608
Kulaga HM et al (2004) Loss of BBS proteins causes anosmia in humans and defects in olfactory cilia structure and function in the mouse. Nat Genet 36:994–998
Li Y, Hu J (2015) Small GTPases act as cellular switches in the context of Cilia. In: Schatten H (ed) The cytoskeleton in health and disease. Springer, New York
Nauli SM et al (2003) Polycystins 1 and 2 mediate mechanosensation in the primary cilium of kidney cells. Nature Genet 33:129–137
Nussbaum RL, Ellis CE (2003) Alzheimer’s disease and Parkinson’s disease. N Engl J Med 348:1356–1364
Peters JM (2002) The anaphase-promoting complex: proteolysis in mitosis and beyond. Mol Cell 9:931–943
Pickart CM, Cohen RE (2004) Proteasomes and their kin: proteases in the machine age. Nature Rev Mol Cell Biol 5:177–187
Quarmby LM, Parker JDK (2005) Cilia and the cell cycle? J Cell Biol 169(5):707–710
Rios RM, Sanchis A, Tassin AM, Fedriani C, Bornens M (2004) GMAP-210 recruits gamma-tubulin complexes to cis-Golgi membranes and is required for Golgi ribbon formation. Cell 118:323–335. https://doi.org/10.1016/j.cell.2004.07.012
Sathasivam K et al (2001) Centrosome disorganization in fibroblast cultures derived from R6/2 Huntington’s disease (HD) transgenic mice and HD patients. Hum Mol Genet 10:2425–2435
Schatten H (2008) The mammalian centrosome and its functional significance. Histochem Cell Biol 129:667–686
Schatten H, Sun QY (2018) Functions and dysfunctions of the mammalian centrosome in health, disorders, disease, and aging. Histochem Cell Biol 150:303–325. https://doi.org/10.1007/s00418-018-1698-1
Shimura H et al (2000) Familial Parkinson disease gene product, parkin, is a ubiquitin-protein ligase. Nat Genet 25:302–305
Takahashi H et al (1994) Familial juvenile parkinsonism: clinical and pathologic study in a family. Neurology 44:437–441
Walsh CA (1999) Genetic malformations of the human cerebral cortex. Neuron 23:19–29
Wigley WC, Fabunmi RP, Lee MG, Marino CR, Muallem S, DeMartino GN, Thomas PJ (1999) Dynamic association of proteasomal machinery with the centrosome. J Cell Biol 145:481–490
Wojcik C, Schroeter D, Wilk S, Lamprecht J, Paweletz N (1996) Ubiquitin-mediated proteolysis centers in HeLa cells: indication from studies of an inhibitor of the chymotrypsin-like activity of the proteasome. Eur J Cell Biol 71:311–318
Wynshaw-Boris A, Gambello MJ (2001) LIS1 and dynein motor function in neuronal migration and development. Genes Dev 15:639–651
Yoder BK, Hou X, Guay-Woodford LM (2002) The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol 13:2508–2516
Zhao J, Ren Y, Jiang Q, Feng J (2003) Parkin is recruited to the centrosome in response to inhibition of proteasomes. J Cell Sci 116:4011–4019
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
Copyright information
© 2022 The Author(s), under exclusive license to Springer Nature Switzerland AG
About this chapter
Cite this chapter
Schatten, H. (2022). Centrosome as Center for Proteolytic Activity and Dysfunctions Associated with Pathogenesis of Human Disease. In: The Centrosome and its Functions and Dysfunctions. Advances in Anatomy, Embryology and Cell Biology, vol 235. Springer, Cham. https://doi.org/10.1007/978-3-031-20848-5_3
Download citation
DOI: https://doi.org/10.1007/978-3-031-20848-5_3
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-031-20847-8
Online ISBN: 978-3-031-20848-5
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)