Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.6794
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dc.titleUse of a novel cytotoxic HEXIM1 peptide in the directed breast cancer therapy
dc.contributor.authorNeo, S.H
dc.contributor.authorLew, Q.J
dc.contributor.authorKoh, S.M
dc.contributor.authorZheng, L
dc.contributor.authorBi, X
dc.contributor.authorChao, S.-H
dc.date.accessioned2020-10-27T05:30:36Z
dc.date.available2020-10-27T05:30:36Z
dc.date.issued2016
dc.identifier.citationNeo, S.H, Lew, Q.J, Koh, S.M, Zheng, L, Bi, X, Chao, S.-H (2016). Use of a novel cytotoxic HEXIM1 peptide in the directed breast cancer therapy. Oncotarget 7 (5) : 5483-5494. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.6794
dc.identifier.issn19492553
dc.identifier.urihttps://scholarbank.nus.edu.sg/handle/10635/180864
dc.description.abstractHexamethylene bisacetamide-inducible protein 1 (HEXIM1) is best known as the inhibitor of positive transcription elongation factor b (P-TEFb) and is recently identified as a novel positive regulator of p53. We previously showed the basic region (BR) of HEXIM1 mediates the binding of HEXIM1 to a nucleolar protein, nucleophosmin (NPM), and can be ubiquitinated by human double minute 2 protein. Here we identify a cytotoxic peptide derived from the BR of HEXIM1. When fused with a cell-penetrating peptide, the HEXIM1 BR peptide triggers rapid cytotoxic effect independent of p53. Similarly, when the BR peptide is linked with a breast cancer cell targeting peptide, LTV, the LTV-BR fusion peptide exhibits specific killing of breast cancer cells, which is not observed with the commonly used cytotoxic peptide, KLA. Importantly, the BR peptide fails to enter cells by itself and does not induce any cytotoxic effects when it is not guided by any cell-penetrating or cancer targeting peptides. We showed that HEXIM1 BR peptide depolarizes mitochondrial membrane potential in a p53-dependent manner and its cell-killing activity is not suppressed by caspase inhibition. Furthermore, we observed an accumulation of the internalized BR peptide in the nucleoli of treated cells and an altered localization of NPM. These results illustrate a novel mechanism which the BR peptide induces cell death and can potentially be used as a novel therapeutic strategy against breast cancer.
dc.rightsAttribution 4.0 International
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceUnpaywall 20201031
dc.subjectantineoplastic agent
dc.subjectcaspase
dc.subjectcell penetrating peptide
dc.subjecthexamethylene bisacetamide inducible protein 1 basic region peptide
dc.subjecthybrid protein
dc.subjectnucleophosmin
dc.subjectpositive transcription elongation factor b
dc.subjectprotein p53
dc.subjectunclassified drug
dc.subjectHEXIM1 protein, human
dc.subjectpeptide fragment
dc.subjectprotein p53
dc.subjectRNA binding protein
dc.subjectTP53 protein, human
dc.subjectapoptosis
dc.subjectArticle
dc.subjectbreast cancer
dc.subjectcell killing
dc.subjectcellular distribution
dc.subjectcontrolled study
dc.subjectdrug cytotoxicity
dc.subjecthuman
dc.subjecthuman cell
dc.subjectinternalization
dc.subjectmembrane depolarization
dc.subjectmitochondrial membrane potential
dc.subjectnucleolus
dc.subjectprotein expression
dc.subjectantagonists and inhibitors
dc.subjectapoptosis
dc.subjectBreast Neoplasms
dc.subjectcell proliferation
dc.subjectfemale
dc.subjectfluorescent antibody technique
dc.subjectgenetic transcription
dc.subjectgenetics
dc.subjectmetabolism
dc.subjectpathology
dc.subjecttumor cell culture
dc.subjectWestern blotting
dc.subjectApoptosis
dc.subjectBlotting, Western
dc.subjectBreast Neoplasms
dc.subjectCell Proliferation
dc.subjectFemale
dc.subjectFluorescent Antibody Technique
dc.subjectHumans
dc.subjectPeptide Fragments
dc.subjectRNA-Binding Proteins
dc.subjectTranscription, Genetic
dc.subjectTumor Cells, Cultured
dc.subjectTumor Suppressor Protein p53
dc.typeArticle
dc.contributor.departmentDEPT OF MICROBIOLOGY & IMMUNOLOGY
dc.description.doi10.18632/oncotarget.6794
dc.description.sourcetitleOncotarget
dc.description.volume7
dc.description.issue5
dc.description.page5483-5494
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