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    A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.

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    Authors
    Baker, Rachael D.
    Howl, John D.
    Nicholl, Iain D.
    Issue Date
    2007
    
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    Abstract
    Targeting chemotherapeutic agents directly to sites of DNA replication and repair within cancerous cells is problematic. This study attempts to address the issue of nuclear delivery of biologically active peptides with the potential to disrupt cancer cell growth. Herein, the protein transduction domain of the HIV-1 transactivator of transcription, Tat (Tat(48-60)), is used to deliver a cytotoxic peptide mimic of the cyclin-dependent kinase inhibitor, p21(WAF1/CIP1) into the nucleus. This construct, which we designate as Tat(48-60)-P10, contains the PCNA interacting protein (PIP) box. We demonstrate the utility of Tat(48-60) for peptide delivery to the nucleus and show that Tat(48-60)-P10 induces apoptosis specific to the inclusion of the wild type PIP box containing sequence. Colocalization of Tat(48-60)-P10 with nuclear PCNA was observed by immunofluorescence analysis, supporting the hypothesis that cytotoxicity is potentially related to disruption of nuclear PCNA function. The U251 and U373 glioma cell lines exhibited particular sensitivity to the construct.
    Citation
    Peptides, 28(4): 731-740
    Publisher
    Amsterdam: Elsevier
    Journal
    Peptides
    URI
    http://hdl.handle.net/2436/29932
    DOI
    10.1016/j.peptides.2006.12.013
    PubMed ID
    17287047
    Additional Links
    http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T0M-4MNR0FX-2&_user=10&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000050221&_version=1&_urlVersion=0&_userid=10&md5=ec79700027ca9d2d394c5d24af7137c3
    Type
    Journal article
    Language
    en
    ISSN
    0196-9781
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.peptides.2006.12.013
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