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The Potential Role of Krüppel-Like Zinc-Finger Protein Glis3 in Genetic Diseases and Cancers

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Archivum Immunologiae et Therapiae Experimentalis Aims and scope

Abstract

Gli-similar 3 (Glis3) belongs to a Glis subfamily of Krüppel-like zinc-finger transcription factors characterized to regulate a set of downstream targets essential for cellular functions, including pancreatic development, β-cell maturation and maintenance, and insulin production. Examination of the DNA-binding domain of Glis3 reveals that this domain contains a repeated cysteine 2/histidine 2 (Cys2/His2) zinc-finger motif in the central region where the recognized DNA sequence binds. The loss of the production of pancreatic hormones, such as insulin 1 and 2, is linked to the down-regulation of β cells-related genes and promotes the apoptotic death of β cells found in mutant Glis3. Although accumulating studies converge on the Glis3 functioning in β cells, recently, there have been developments in the field of Glis3 using knockdown/mutant mice to better understand the role of Glis3 in diseases. The Glis3 mutant mice have been characterized for their propensity to develop congenital hypothyroidism, polycystic kidney disease, and some types of cancer. In this review, we attempt to comprehensively summarize the knowledge of Glis3, including its structure and general function in cells. We also collected and organized the academic achievements related to the possible mechanisms of Glis3-related diseases.

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Acknowledgements

The study was supported by Grant MOST105-2311-B-037-001 from the Ministry of Science and Technology (MOST), Taiwan; Grant KMU-TP104A3 and KMU-TP105A7 from Kaohsiung Medical University, Taiwan; Grant NSYSU-KMU104-P031, NSYSU-KMU105-P017 and KMU106-P019 from NSYSU-KMU Joint Research Project; and grant Aim for the Top Universities Grant.

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  1. Chon-Kit Chou and Chin-Ju Tang contributed equally to this work.

Authors and Affiliations

  1. Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Chon-Kit Chou

  2. Department of Biotechnology, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Chon-Kit Chou, Chin-Ju Tang, Han-Lin Chou, Chun-Yen Liu, Ming-Chong Ng, Yu-Ting Chang & Chien-Chih Chiu

  3. Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung, 804, Taiwan

    Chien-Chih Chiu

  4. Translational Research Center and Department of Medical Research, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Shyng-Shiou F. Yuan & Chien-Chih Chiu

  5. Research Center for Environment Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan

    Eing-Mei Tsai & Chien-Chih Chiu

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  1. Chon-Kit Chou
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Chou, CK., Tang, CJ., Chou, HL. et al. The Potential Role of Krüppel-Like Zinc-Finger Protein Glis3 in Genetic Diseases and Cancers. Arch. Immunol. Ther. Exp. 65, 381–389 (2017). https://doi.org/10.1007/s00005-017-0470-x

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