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Dishevelled proteins and CYLD reciprocally regulate each other in CML cell lines

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Abstract

Dishevelled (Dvl) proteins are activated by Wnt pathway stimulation and have crucial roles in the regulation of β-catenin destruction complex. CYLD is a tumor suppressor and a deubiquitination enzyme. CYLD negatively regulates the Wnt/β-catenin signaling pathway by deubiquitinating Dvl proteins. Loss of function and mutations of CYLD were linked to different types of solid tumors. Loss of function in CYLD is associated with Dvl hyper ubiquitination, resulting in the transmission of Wnt signaling to downstream effectors. β-catenin upregulation is observed during disease progression in chronic myeloid leukemia (CML). Deregulated Dvl signaling may be a reason for β-catenin activation in CML; and CYLD may contribute to Dvl deregulation. First, we evaluated mRNA expression in three CML cell lines and mRNA expression of the CYLD gene was found to be present in all (K562, MEG01, KU812). Unlike solid tumors sequencing revealed no mutations in the coding sequences of the CYLD gene. DVL genes were silenced by using a pool of siRNA oligonucleotides and gene expression differences in CYLD was determined by RT-PCR and western blot. CYLD protein expression decreased after Dvl silencing. An opposite approach of overexpressing Dvl proteins resulted in upregulated CYLD expression. While previous reports have described CYLD as a regulator of DVL proteins; our data suggests the presence of a more complicated reciprocal regulatory mechanism in CML cell lines.

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Acknowledgements

This study was financially supported by The Scientific and Technological Research Council of Turkey (TUBITAK) (Project Code: 1001, Grant Number: 114Z225).

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Author notes

  1. Ceyda Çalışkan

    Present address: Department of Molecular Biology, Izmir Institute of Technology, Balcova, 35340, Izmir, Turkey

  2. Melek Pehlivan

    Present address: Vocational School of Health Sciences, Izmir Katip Celebi University, Izmir, Turkey

Authors and Affiliations

  1. Department of Medical Biology and Genetics, Faculty of Medicine, Dokuz Eylul University, Balcova, 35340, Izmir, Turkey

    Ceyda Çalışkan, Melek Pehlivan, Zeynep Yüce & Ogun Sercan

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  1. Ceyda Çalışkan
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  2. Melek Pehlivan
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Correspondence to Ogun Sercan.

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Çalışkan, C., Pehlivan, M., Yüce, Z. et al. Dishevelled proteins and CYLD reciprocally regulate each other in CML cell lines. Mol Biol Rep 44, 391–397 (2017). https://doi.org/10.1007/s11033-017-4122-3

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  • DOI: https://doi.org/10.1007/s11033-017-4122-3

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