ZFP226 is a novel artificial transcription factor for selective activation of tumor suppressor KIBRA

KIBRA has been suggested as a key regulator of the hippo pathway, regulating organ size, cell contact inhibition as well as tissue regeneration and tumorigenesis. Recently, alterations of KIBRA expression caused by promotor methylation have been reported for several types of cancer. Our current stud...

Authors: Schelleckes, Katrin
Schmitz, Boris
Lenders, Malte
Mewes, Mirja
Brand, Stefan-Martin
Brand, Eva
Division/Institute:FB 13: Biologie
FB 05: Medizinische Fakultät
Document types:Article
Media types:Text
Publication date:2018
Date of publication on miami:02.05.2019
Modification date:02.05.2019
Edition statement:[Electronic ed.]
Source:Scientific Reports 8 (2018) 4230, 1-9
DDC Subject:610: Medizin und Gesundheit
License:CC BY 4.0
Language:English
Funding:Finanziert durch den Open-Access-Publikationsfonds 2018 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format:PDF document
URN:urn:nbn:de:hbz:6-25119485637
Permalink:http://nbn-resolving.de/urn:nbn:de:hbz:6-25119485637
Other Identifiers:DOI: 10.1038/s41598-018-22600-6
Digital documents:artikel_brand_2018.pdf

KIBRA has been suggested as a key regulator of the hippo pathway, regulating organ size, cell contact inhibition as well as tissue regeneration and tumorigenesis. Recently, alterations of KIBRA expression caused by promotor methylation have been reported for several types of cancer. Our current study aimed to design an artificial transcription factor capable of re-activating expression of the tumor suppressor KIBRA and the hippo pathway. We engineered a new gene named ‘ZFP226′ encoding for a ~23 kDa fusion protein. ZFP226 belongs to the Cys2-His2 zinc finger type and recognizes a nine base-pair DNA sequence 5′-GGC-GGC-GGC-3′ in the KIBRA core promoter P1a. ZFP226 showed nuclear localization in human immortalized kidney epithelial cells and activated the KIBRA core promoter (p