School 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.
Key Laboratory of Immunology in Universities of Shangdong Province, Weifang Medical University, Weifang, Shandong Province 261053, China.
Biochim Biophys Acta Rev Cancer. 2022 May;1877(3):188731. doi: 10.1016/j.bbcan.2022.188731. Epub 2022 Apr 25.
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.
Kruppel 相关盒（KRAB）锌指蛋白（KRAB-ZFPs）是哺乳动物细胞中最大的转录/转录调节因子家族。KRAB-ZFPs 的典型结构特征是氨基末端的 KRAB 结构域，它招募其他转录调节蛋白，以及羧基末端的 C2H2 锌指基序，它与特定的 DNA 序列结合。许多 KRAB-ZFPs 在几种癌症类型中异常表达，并参与许多与癌症相关的信号通路和生物过程，包括细胞增殖、凋亡、迁移、侵袭和转移。在这篇综述中，我们总结了参与转录调节的蛋白质结构和机制，并重点介绍了 KRAB-ZFPs 调节的多个关键信号通路，包括 p53、Wnt/β-catenin 和 NF-κB 通路，强调了 KRAB-ZFPs 在不同癌症中的致癌和抑癌作用。我们还讨论了调节 KRAB-ZFP 表达的机制。进一步阐明 KRAB-ZFPs 的致癌和抑癌作用及其针对多种协同信号通路的靶向治疗可能对有效的癌症治疗具有重要价值。
