A sychnological cell penetrating peptide mimic of p21(WAF1/CIP1) is pro-apoptogenic.
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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.
CitationPeptides, 28(4): 731-740
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- Authors: Dennison SR, Baker RD, Nicholl ID, Phoenix DA
- Issue date: 2007 Nov 9
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- Authors: Yoshikawa T, Sugita T, Mukai Y, Yamanada N, Nagano K, Nabeshi H, Yoshioka Y, Nakagawa S, Abe Y, Kamada H, Tsunoda S, Tsutsumi Y
- Issue date: 2008 Jul 25
- [Cytotoxicity of chimera peptides incorporating sequences of cyclin kinases inhibitors].
- Authors: Kharchenko VP, Kulinich VG, Lunin VG, Filiasova EI, Shishkin AM, Sergeenko OV, Riazanova EM, Voronina OL, Bozhenko VK
- Issue date: 2007
- Nuclear translocation of p21(WAF1/CIP1) protein prior to its cytosolic degradation by UV enhances DNA repair and survival.
- Authors: Lee JY, Kim HS, Kim JY, Sohn J
- Issue date: 2009 Dec 25
- Cyclosporine A inhibits colorectal cancer proliferation probably by regulating expression levels of c-Myc, p21(WAF1/CIP1) and proliferating cell nuclear antigen.
- Authors: Masuo T, Okamura S, Zhang Y, Mori M
- Issue date: 2009 Nov 18