2018 - Sustainable Industrial Processing Summit & Exhibition
4-7 November 2018, Rio Othon Palace, Rio De Janeiro, Brazil
Seven Nobel Laureates have already confirmed their attendance: Prof. Dan Shechtman, Prof. Sir Fraser Stoddart, Prof. Andre Geim, Prof. Thomas Steitz, Prof. Ada Yonath, Prof. Kurt Wüthrich and Prof. Ferid Murad. More than 400 Abstracts Submitted from about 60 Countries.
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    Identification of a Peptide that can Enhance Genotoxic Sensitivity Through Cellular Redistribution of Chk1 Protein
    Kwang Seok Kim1; Sang Jun Park1; Chun-ho Kim1;
    1KIRAMS, Seoul, South Korea;
    PAPER: 414/Manufacturing/Regular (Oral)
    SCHEDULED: 15:15/Tue./Sao Conrado (50/2nd)



    ABSTRACT:
    Chk1 protein has been a target in the detectable genotoxic sensitivity of cells and tissues, and a major focus of pharmaceutical development to enhance sensitivity of tumor cells to chemo- and radiotherapy [1]. To take advantage of such biological effects, we identified a specific Chk1-binding 12-mer peptide from screening of phage display library and characterized the peptide in terms of cellular cytotoxicity, and effect on Chk1 activity, and sensitivity to genotoxic agents [2]. Interestingly, polyarginine-mediated internalization of the peptide redistributed nuclear Chk1 with prominent decrease in the nucleus in the absence of DNA damage. Treatment of HeLa cervical cancer cells or NCI-H460 lung cancer cells with the peptide significantly enhanced radiation sensitivity following ionizing radiation (IR). Moreover, IR-induced Chk1 destabilization was aggravated by Chk1 peptide treatment. The approach using the specific Chk1 peptide may facilitate a mechanistic understanding and potential modulation of Chk1 activities and provide a novel rationale for development of specific Chk1-targeting agents [3-4].

    References:
    1. Zhang Y, Hunter T. Roles of Chk1 in cell biology and cancer therapy. Int J Cancer. 2014;134(5):1013-23
    2. KS Kim, KJ Choi, SW Bae. A novel Chk1-binding peptide that can enhance genotoxic sensitivity through cellular redistribution of nuclear Chk1. 2016. Int J Mol Med 38:1490-1498
    3. Saladin A, Rey J, Thevenet P, Zacharias M, Moroy G, Tuffery P. PEP-SiteFinder: a tool for the blind identification of peptide binding sites on protein surfaces. Nucleic Acids Res. 2014;42:W221-6.
    4. Kawabe T. G2 checkpoint abrogators as anticancer drugs. Mol Cancer Ther 2004; 3:513-9.