Harmeyer Kayla M, Facompre Nicole D, Herlyn Meenhard, Basu Devraj
Department of Otorhinolaryngology-Head and Neck Surgery, University of Pennsylvania, Philadelphia, PA 19104, USA.
The Wistar Institute, Philadelphia, PA 19104, USA.
Trends Cancer. 2017 Oct;3(10):713-725. doi: 10.1016/j.trecan.2017.08.004. Epub 2017 Sep 12.
JARID1 proteins are histone demethylases that both regulate normal cell fates during development and contribute to the epigenetic plasticity that underlies malignant transformation. This H3K4 demethylase family participates in multiple repressive transcriptional complexes at promoters and has broader regulatory effects on chromatin that remain ill-defined. There is growing understanding of the oncogenic and tumor suppressive functions of JARID1 proteins, which are contingent on cell context and the protein isoform. Their contributions to stem cell-like dedifferentiation, tumor aggressiveness, and therapy resistance in cancer have sustained interest in the development of JARID1 inhibitors. Here we review the diverse and context-specific functions of the JARID1 proteins that may impact the utilization of emerging targeted inhibitors of this histone demethylase family in cancer therapy.
JARID1蛋白是组蛋白去甲基化酶，在发育过程中调节正常细胞命运，并促成恶性转化所依赖的表观遗传可塑性。这个H3K4去甲基化酶家族参与启动子处的多个抑制性转录复合物，对染色质具有更广泛的调节作用，但其作用仍不明确。人们对JARID1蛋白的致癌和抑癌功能的认识不断加深，这些功能取决于细胞背景和蛋白异构体。它们在癌症中对干细胞样去分化、肿瘤侵袭性和治疗抗性的作用，持续引发了对JARID1抑制剂开发的关注。在此，我们综述了JARID1蛋白多样且依赖背景的功能，这些功能可能会影响这种组蛋白去甲基化酶家族新型靶向抑制剂在癌症治疗中的应用。
