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Wolverhampton Intellectual Repository and E-Theses > Research Institutes > Research Institute in Healthcare Science > Molecular Pharmacology Research Group > A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.

Please use this identifier to cite or link to this item: http://hdl.handle.net/2436/29932
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Title: A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.
Authors: Baker, Rachael D.
Howl, John D.
Nicholl, Iain D.
Citation: Peptides, 28(4): 731-740
Publisher: Amsterdam: Elsevier
Journal: Peptides
Issue Date: 2007
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
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.
Type: Article
Language: en
Keywords: Cell Penetrating Peptides (CPP)
Molecular Biology
PCNA
Tat
Chemotherapeutic targets
MeSH: Amino Acid Sequence
Apoptosis
Cell Line, Tumor
Cell Nucleus
Cell Survival
Cyclin-Dependent Kinase Inhibitor p21
Dose-Response Relationship, Drug
Gene Products, tat
Humans
Immunoblotting
In Situ Nick-End Labeling
Molecular Sequence Data
Peptides
Proliferating Cell Nuclear Antigen
Protein Binding
ISSN: 0196-9781
Appears in Collections: Molecular Pharmacology Research Group
Cancer Research Group

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