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| 1 | Nuclear Aurora kinase A switches m^(6)A reader YTHDC1 to enhance an oncogenic RNA splicing of tumor suppressor RBM4显示文摘Aberrant RNA splicing produces alternative isoforms of genes to facilitate tumor progression,yet how this process is regulated by oncogenic signal remains largely unknown.Here,we unveil that non-canonical activation of nuclear AURKA promotes an oncogenic RNA splicing of tumor suppressor RBM4 directed by m^(6)A reader YTHDC1 in lung cancer.Nuclear translocation of AURKA is a prerequisite for RNA aberrant splicing,specifically triggering RBM4 splicing from the full isoform(RBM4-FL)to the short isoform(RBM4-S)in a kinase-independent manner. | SiSi Li YangFan Qi JiaChuan Yu YuChao Hao Bin He MengJuan Zhang ZhenWei Dai TongHui Jiang SuYi Li Fang Huang Ning Chen Jing Wang MengYing Yang DaPeng Liang Fan An JinYao Zhao WenJun Fan YuJia Pan ZiQian Deng YuanYuan Luo Tao Guo Fei Peng ZhiJie Hou ChunLi Wang FeiMeng Zheng LingZhi Xu Jie Xu QingPing Wen BiLian Jin Yang Wang Quentin Liu | 2022 | Signal Transduction and Targeted Therapy2022，7，5： | 4 |
| 2 | Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway显示文摘Increasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits.However,the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated.We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis.In the current study,we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat.Fat-specific knockout of Rheb decreased protein kinase A(PKA)activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice.On the other hand,overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes.Mechanistically,Rheb overexpression in brown adipocytes increased Notch expression,leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation.Our study demonstrates that Rheb,by selectively modulating thermogenic gene expression in brown and beige adipose tissues,plays an important role in regulating energy homeostasis. | Wen Meng Xiuci Liang Ting Xiao Jing Wang Jie Wen Hairong Luo Jianhui Teng Yanquan Fei Qinghai Zhang Bilian Liu Fang Hu juli Bai Meilian Liu Zhiguang Zhou Feng Liu | 2019 | Journal of Molecular Cell Biology2019，11，9： | 2 |
| 3 | GRB10 regulates β-cell mass by inhibiting β-cell proliferation and stimulating β-cell dedifferentiation显示文摘Decreased functional β-cell mass is the hallmark of diabetes, but the cause of this metabolic defect remains elusive. Here, we show that the levels of the growth factor receptor-bound protein 10(GRB10), a negative regulator of insulin and m TORC1 signaling, are markedly induced in islets of diabetic mice and high glucose-treated insulinoma cell line INS-1 cells. β-cell-specific knockout of Grb10 in mice increased β-cell mass and improved β-cell function. Grb10-deficient β-cells exhibit enhanced m TORC1 signaling and reduced β-cell dedifferentiation, which could be blocked by rapamycin. On the contrary, Grb10 overexpression induced β-cell dedifferentiation in MIN6 cells. Our study identifies GRB10 as a critical regulator of β-cell dedifferentiation and β-cell mass, which exerts its effect by inhibiting m TORC1 signaling. | Zixin Cai Fen Liu Yan Yang Dandan Li Shanbiao Hu Lei Song Shaojie Yu Ting Li Bilian Liu Hairong Luo Weiping Zhang Zhiguang Zhou Jingjing Zhang | 2022 | Journal of Genetics and Genomics2022，49，3： | 1 |
| 4 | Myeloid adrenerglc signaling via CaMKII forms a feedforward loop of catecholarnine biosynthesis显示文摘 | Yan Luo Bilian Liu Xin Yang Xiaoxiao Ma Xing Zhang Denis E. Bragin Xuexian O. Yang Wendong Huang Meilian Liu | 2017 | Journal of Molecular Cell Biology2017，9，5： | 1 |
| 5 | Cancer cell employs a microenvironmental neural signal transactivating nucleus-mitochondria coordination to acquire stemness显示文摘Cancer cell receives extracellular signal inputs to obtain a stem-like status,yet how tumor microenvironmental(TME)neural signals steer cancer stemness to establish the hierarchical tumor architectures remains elusive.Here,a pan-cancer transcriptomic screening for 10852 samples of 33 TCGA cancer types reveals that cAMP-responsive element(CRE)transcription factors are convergent activators for cancer stemness.Deconvolution of transcriptomic profiles,specification of neural markers and illustration of norepinephrine dynamics uncover a bond between TME neural signals and cancer-cell CRE activity.Specifically,neural signal norepinephrine potentiates the stemness of proximal cancer cells by activating cAMP-CRE axis,where ATF1 serves as a conserved hub.Upon activation by norepinephrine,ATF1 potentiates cancer stemness by coordinated trans-activation of both nuclear pluripotency factors MYC/NANOG and mitochondrial biogenesis regulators NRF1/TFAM,thereby orchestrating nuclear reprograming and mitochondrial rejuvenating.Accordingly,single-cell transcriptomes confirm the coordinated activation of nuclear pluripotency with mitochondrial biogenesis in cancer stem-like cells.These findings elucidate that cancer cell acquires stemness via a norepinephrine-ATF1 driven nucleus-mitochondria collaborated program,suggesting a spatialized stemness acquisition by hijacking microenvironmental neural signals. | Bin He Rui Gao Shasha Lv Ailin Chen Junxiu Huang Luoxuan Wang Yunxiu Feng Jiesi Feng Bing Liu Jie Lei Bing Deng Bin He Bai Cui Fei Peng Min Yan Zifeng Wang Eric W-F Lam Bilian Jin Zhiming Shao Yulong Li Jianwei Jiao Xi Wang Quentin Liu | 2023 | Signal Transduction and Targeted Therapy2023，8，8： | 0 |
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