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The signaling pathways regulated by KRAB zinc-finger proteins in cancer
Mengying Sun1, Jiyu Ju2, Yue Ding3
1School of Life science and Technology, Weifang Medical University, Weifang, Shandong Province 261053, China; State Key Laboratory of Proteomics, Beijing Proteome Research Center, National Center for Protein Sciences (Beijing), Beijing Institute of Lifeomics, Beijing 102206, China.
Abstract:
Kruppel-associated box (KRAB) zinc-finger proteins (KRAB-ZFPs) are the largest transcriptional/transcription-regulatory factor family in mammalian cells. The amino-terminal KRAB domain, which recruits other transcription-regulating proteins, and the carboxyl-terminal C2H2 zinc-finger motifs, which bind to specific DNA sequences, are the typical structural characteristics of KRAB-ZFPs. Many KRAB-ZFPs are abnormally expressed in several cancer types and involved in many cancer-related signaling pathways and bioprocesses, including cell proliferation, apoptosis, migration, invasion, and metastasis. In this review, we summarize the protein structure and mechanisms involved in transcriptional regulation, and focus on multiple key signaling pathways regulated by KRAB-ZFPs, including the p53, Wnt/β-catenin, and NF-κB pathways, highlighting the oncogenic and tumor-suppressive roles of KRAB-ZFPs in different cancers. We also discuss the mechanisms regulating KRAB-ZFP expression. The further elucidation of the oncogenic and tumor-suppressive roles of KRAB-ZFPs and their targeting for multiple synergistic signaling pathways may be valuable for effective cancer therapy.
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