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dc.contributor.authorBaker, Rachael D.
dc.contributor.authorHowl, John D.
dc.contributor.authorNicholl, Iain D.
dc.date.accessioned2008-06-12T08:24:54Z
dc.date.available2008-06-12T08:24:54Z
dc.date.issued2007
dc.identifier.citationPeptides, 28(4): 731-740
dc.identifier.issn0196-9781
dc.identifier.pmid17287047
dc.identifier.doi10.1016/j.peptides.2006.12.013
dc.identifier.urihttp://hdl.handle.net/2436/29932
dc.description.abstractTargeting 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.
dc.language.isoen
dc.publisherAmsterdam: Elsevier
dc.relation.urlhttp://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
dc.subjectCell Penetrating Peptides (CPP)
dc.subjectMolecular Biology
dc.subjectPCNA
dc.subjectTat
dc.subjectChemotherapeutic targets
dc.subject.meshAmino Acid Sequence
dc.subject.meshApoptosis
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Nucleus
dc.subject.meshCell Survival
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21
dc.subject.meshDose-Response Relationship, Drug
dc.subject.meshGene Products, tat
dc.subject.meshHumans
dc.subject.meshImmunoblotting
dc.subject.meshIn Situ Nick-End Labeling
dc.subject.meshMolecular Sequence Data
dc.subject.meshPeptides
dc.subject.meshProliferating Cell Nuclear Antigen
dc.subject.meshProtein Binding
dc.titleA sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.
dc.typeArticle
dc.identifier.journalPeptides
html.description.abstractTargeting 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.


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