Cytosolic PrP induces apoptosis of cell by disrupting microtubule assembly.

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  • Additional Information
    • Source:
      Publisher: Humana Press Country of Publication: United States NLM ID: 9002991 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1559-1166 (Electronic) Linking ISSN: 08958696 NLM ISO Abbreviation: J Mol Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: Totowa, NJ : Humana Press
      Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989-
    • Subject Terms:
      Apoptosis/*physiology ; Cytosol/*metabolism ; Microtubules/*metabolism ; Prions/*metabolism; Animals ; Cricetinae ; HeLa Cells ; Humans ; Mesocricetus ; Prions/genetics ; Scrapie/metabolism ; Scrapie/pathology
    • Abstract:
      Prion protein (PrP) is able to bind with tubulin and to interfere with the formation of microtubule. To investigate the influence of accumulation of cytosolic PrP in cytoplasm on microtubule, plasmid pcDNA3.1-PrP23-230 expressing human PrP23-230 was introduced into HeLa cells. Immunoprecipitation assays identified the molecular interaction between cytosolic PrP and cellular tubulin. Confocal microscopy showed the co-localization of the expressed cytosolic PrP with tubulin in cytoplasm. Immunofluorescent assays of tubulin illustrated remarkable disruption of microtubular structures in the cells accumulated with cytosolic PrP. Meanwhile, the expressed cytosolic PrP significantly reduced cell viability and induced cell apoptosis. The amounts of microtubule protein in the cells expressing cytosolic PrP were decreased. Moreover, the levels of endogenous tubulin in the brain tissues of scrapie-infected hamsters were significantly lower than that of normal one. It highlights a close linkage between disruption of microtubule framework and cell death caused by abnormal presence of cellular PrP in cytoplasm. The association of apoptosis with microtubule-disrupting activity caused by cytosolic PrP may further provide insight into the unresolved biological function of PrP in the neurons.
    • References:
      Curr Cancer Drug Targets. 2007 Dec;7(8):713-29. (PMID: 18220532)
      Biochemistry. 1990 Jun 5;29(22):5405-12. (PMID: 1974460)
      Cell. 2005 Apr 22;121(2):195-206. (PMID: 15851027)
      Biochem Biophys Res Commun. 2004 Jan 16;313(3):818-23. (PMID: 14697265)
      Mol Biol Rep. 2010 Oct;37(7):3183-92. (PMID: 19826908)
      Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13363-83. (PMID: 9811807)
      Biochem Biophys Res Commun. 2005 Aug 26;334(2):403-11. (PMID: 16004966)
      J Med Case Rep. 2008 Oct 17;2:331. (PMID: 18925969)
      J Clin Pharm Ther. 2002 Oct;27(5):313-20. (PMID: 12383131)
      J Vet Med B Infect Dis Vet Public Health. 2005 Dec;52(10):437-43. (PMID: 16364019)
      Nat Rev Mol Cell Biol. 2001 Feb;2(2):118-26. (PMID: 11252953)
      Oncogene. 2004 Jul 29;23(34):5781-91. (PMID: 15208671)
      BMC Infect Dis. 2010 Apr 01;10:86. (PMID: 20356412)
      J Mol Neurosci. 2011 Mar;43(3):225-34. (PMID: 20526696)
      Neurology. 2005 Apr 26;64(8):1455-7. (PMID: 15851745)
      Apoptosis. 2003 Oct;8(5):413-50. (PMID: 12975575)
      J Neurosci. 2003 Aug 6;23(18):7183-93. (PMID: 12904479)
      J Neurobiol. 2004 Feb 5;58(2):258-71. (PMID: 14704957)
      J Cell Biol. 2004 Mar 15;164(6):803-9. (PMID: 15024029)
      Mol Cell Biochem. 2008 Mar;310(1-2):49-55. (PMID: 18038270)
      Front Biosci. 1996 Aug 01;1:d118-30. (PMID: 9159219)
      Cell. 1987 Oct 23;51(2):229-40. (PMID: 2444340)
      J Neurochem. 2000 Nov;75(5):1889-97. (PMID: 11032878)
      J Biol Chem. 2001 Jan 26;276(4):2427-31. (PMID: 11069909)
      Biochem Biophys Res Commun. 2006 Oct 13;349(1):391-9. (PMID: 16934224)
      Proteins. 2009 Nov 1;77(2):279-96. (PMID: 19422054)
      Nature. 1986 Dec 18-31;324(6098):621. (PMID: 3796729)
      Neuroscience. 2008 Jun 26;154(3):946-52. (PMID: 18495362)
      EMBO J. 2004 Nov 24;23(23):4550-9. (PMID: 15526034)
      Acta Biochim Biophys Sin (Shanghai). 2009 Nov;41(11):929-37. (PMID: 19902127)
      BMB Rep. 2009 Jul 31;42(7):444-9. (PMID: 19643043)
      J Biol Chem. 2006 May 12;281(19):13559-13565. (PMID: 16537534)
      Nat Cell Biol. 2004 Oct;6(10):941-53. (PMID: 15459722)
      Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):14955-60. (PMID: 11742063)
      Arch Biochem Biophys. 2008 Feb 1;470(1):83-92. (PMID: 18037369)
      Science. 2002 Nov 29;298(5599):1781-5. (PMID: 12386337)
      Science. 2004 Jul 30;305(5684):673-6. (PMID: 15286374)
      J Biol Chem. 2005 Jan 7;280(1):317-25. (PMID: 15525638)
    • Accession Number:
      0 (Prions)
    • Publication Date:
      Date Created: 20100915 Date Completed: 20110721 Latest Revision: 20211020
    • Publication Date:
      20231215
    • Accession Number:
      10.1007/s12031-010-9443-9
    • Accession Number:
      20838930