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

2.50
Hdl Handle:
http://hdl.handle.net/2436/29932
Title:
A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.
Authors:
Baker, Rachael D.; Howl, John D.; Nicholl, Iain D.
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
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
Type:
Article
Language:
en
ISSN:
0196-9781
Appears in Collections:
Molecular Pharmacology Research Group; Cancer Research Group

Full metadata record

DC FieldValue Language
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): 731-740en
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.en
dc.language.isoenen
dc.publisherAmsterdam: Elsevieren
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=ec79700027ca9d2d394c5d24af7137c3en
dc.subjectCell Penetrating Peptides (CPP)en
dc.subjectMolecular Biologyen
dc.subjectPCNAen
dc.subjectTaten
dc.subjectChemotherapeutic targetsen
dc.subject.meshAmino Acid Sequenceen
dc.subject.meshApoptosisen
dc.subject.meshCell Line, Tumoren
dc.subject.meshCell Nucleusen
dc.subject.meshCell Survivalen
dc.subject.meshCyclin-Dependent Kinase Inhibitor p21en
dc.subject.meshDose-Response Relationship, Drugen
dc.subject.meshGene Products, taten
dc.subject.meshHumansen
dc.subject.meshImmunoblottingen
dc.subject.meshIn Situ Nick-End Labelingen
dc.subject.meshMolecular Sequence Dataen
dc.subject.meshPeptidesen
dc.subject.meshProliferating Cell Nuclear Antigenen
dc.subject.meshProtein Bindingen
dc.titleA sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.en
dc.typeArticleen
dc.identifier.journalPeptidesen

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