Yeolhoe Kim, Kyung-Tae Lee, Han Byeol Kim, Hyeryeon Jung, Jeong Yeon Ko, Tae Hyun Kweon, Hari Chandana Yadavalli, Junghwa Seo, Suena Ji, Yun Ju Kim, Donghyuk Shin, Seong Wook Yang, Myeong Min Lee, Jin Won Cho, Eugene C Yi, Jin-Wu Nam, Won Ho Yang
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引用次数: 0
Abstract
Non-POU domain-containing octamer-binding protein (NONO) is a multifunctional member of the Drosophila behavior/human splicing (DBHS) protein family with DNA- and RNA-binding activity. NONO is highly expressed in various types of cancer, and excessive O-GlcNAcylation has also been implicated in tumorigenesis. Although recent studies revealed that NONO is O-GlcNAcylated and that this modification is involved in DNA damage repair, it remains unknown whether O-GlcNAcylation of NONO regulates cancer cell proliferation. Additionally, little is known about the effect of O-GlcNAcylation on other biological properties of NONO. In this study, we identify Thr440 as the primary NONO O-GlcNAcylation site and demonstrates its crucial role in the assembly of paraspeckles, an important subnuclear compartment that facilitates NONO-dependent transcriptional regulation in mammalian cells. Moreover, we found that O-GlcNAcylation of NONO is required to maintain the expression of genes related to microtubule cytoskeleton organization involved in mitosis and to suppress the expression of genes related to cellular response to type I interferon. Regarding the regulation of these genes, depletion of NONO O-GlcNAcylation at Thr440 significantly inhibited the proliferation of colon cancer cells. Collectively, our findings highlight NONO O-GlcNAcylation as a key regulator modulating paraspeckle formation and as a candidate therapeutic target in colon cancer.
期刊介绍:
Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary.
Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.