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| 1 | NSD3S stabilizes MYC through hindering its interaction with FBXW7显示文摘The MYC transcription factor plays a key role in cell growth control. Enhanced MYC protein stability has been found to promote tumorigenesis. Thus, understanding how MYC stability is controlled may have significant implications for revealing MYC-driven growth regulatory mechanisms in physiological and pathological processes. Our previous work identified the histone lysine methyltransferase nuclear receptor binding SET domain protein 3 (NSD3) as a MYC modulator. NSD3S, a noncatalytic isoform of NSD3 with oncogenic activity, appears to bind, stabilize, and activate the transcriptional activity of MYC. However, the mechanism by which NSD3S stabilizes MYC remains to be elucidated. To uncover the nature of the interaction and the underlying mechanism of MYC regulation by NSD3S, we characterized the binding interface between both proteins by narrowing the interface to a 15-amino acid region in NSD3S that is partially required for MYC regulation. Mechanistically, NSD3S binds to MYC and reduces the association of F-box and WD repeat domain containing 7 (FBXW7) with MYC, which results in suppression of FBXW7-mediated proteasomal degradation of MYC and an increase in MYC protein half-life. These results support a critical role for NSD3S in the regulation of MYC function and provide a novel mechanism for NSD3S oncogenic function through inhibition of FBXW7-mediated degradation of MYC. | Valentina Gonzalez-Pecchi Albert KKwan Sean Doyle Andrey AIvanov Yuhong Du Haian Fu | 2020 | Journal of Molecular Cell Biology2020，12，6： | 2 |
| 2 | 14-3-3 Proteins Mediate an Essential Anti-apoptotie Signal显示文摘 | SHANE C MASTERS HAIAN FU | 2001 | J Bio Chem(S0021 -9258)2001，276，45： | 1 |
| 3 | Large tumor suppressor 2,LATS2,activates iNK in kinase-independent mechanism through ASK1显示文摘Apoptosis signal-regulating kinase 1 (ASK1)is an important mediator of the cell stress response pathways.Because of its central role in regulating cell death,the activity of ASK1 is tightly regulated by protein-protein interactions and post-translational modifications.Deregulation of ASK1 activity has been linked to human diseases,such as neurological disorders and cancer.Here we describe the identification and characterization of large tumor suppressor 2 (LATS2)as a novel binding partner for ASK1.LATS2 is a core kinase in the Hippo signaling pathway and is commonly downregulated in cancer.We found that LATS2 interacts with ASK1 and increases ASK1-mediated signaUng to promote apoptosis and activate the iNK mitogen-activated protein kinase (MAPK).This change in MAPK signaling is dependent on the catalytic activity of ASK1 but does not require LATS2 kinase activity. This work identifies a novel role for LATS2 as a positive regulator of the ASK1-MKK-JNK signaling pathway and establishes a kinase-independent function of LATS2 that may be part of the intricate regulatory system for cellular response to diverse stress signals. | Lauren Rusnak Cong Tang Qi Qi Xiulei Mo Haian Fu | 2018 | Journal of Molecular Cell Biology2018，10，6： | 1 |
| 4 | 14-3-3 proteins: structure,function,and regulation显示文摘 | Haian Fu Subraraanian RR Masters SC | 2000 | Annu Rev Pharmacol Toxicol2000，40，： | 1 |
| 5 | 14-3-3 Proteins mediate an essential Anti-apoptotic signal显示文摘 | Shane C Masters Haian Fu | 2001 | J Bio Chem2001，276，45： | 1 |
| 6 | Acquisition of taxane resistance by p53 inactivation in ovarian cancer cells显示文摘Ovarian cancer is one of the most common gynecologic malignancies in women and has a poor prognosis.Taxanes are a class of standard first-line chemotherapeutic agents for the treatment of ovarian cancer.However,tumor-intrinsic and acquired resistance to taxanes poses major challenges to improving clinical outcomes.Hence,there is an urgent clinical need to understand the mechanisms of resistance in order to discover potential biomarkers and therapeutic strategies to increase taxane sensitivity in ovarian cancer.Here,we report the identification of an association between the TP53 status and taxane sensitivity in ovarian cancer cells through complementary experimental and informatics approaches.We found that TP53 inactivation is associated with taxane resistance in ovarian cancer cells,supported by the evidence from(i)drug sensitivity profiling with bioinformatic analysis of large-scale cancer therapeutic response and genomic datasets and(ii)gene signature identification based on experimental isogenic cell line models.Further,our studies revealed TP53-dependent gene expression patterns,such as overexpression of ACSM3,as potential predictive biomarkers of taxane resistance in ovarian cancer.The TP53-dependent hyperactivation of the WNT/β-catenin pathway discovered herein revealed a potential vulnerability to exploit in developing combination therapeutic strategies.Identification of this genotype-phenotype relationship between the TP53 status and taxane sensitivity sheds light on TP53-directed patient stratification and therapeutic discoveries for ovarian cancer treatment. | Changfa Shu Xi Zheng Alafate Wuhafu Danielle Cicka Sean Doyle Qiankun Niu Dacheng Fan Kun Qian Andrey AIvanov Yuhong Du Xiulei Mo Haian Fu | 2022 | Acta Pharmacologica Sinica2022，43，9： | 1 |
| 7 | Development of a miniaturized 3D organoid culture platform for ultra-high-throughput screening显示文摘The recent advent of robust methods to grow human tissues as 3D organoids allows us to recapitulate the 3D architecture of tumors in an in vitro setting and offers a new orthogonal approach for drug discovery.However,organoid culturing with extracellular matrix to support 3D architecture has been challenging for high-throughput screening(HTS)-based drug discovery due to technical difficulties.Using genetically engineered human colon organoids as a model system,here we report our effort to miniaturize such 3D organoid culture with extracellular matrix support in high-density plates to enable HTS.We first established organoid culturing in a 384-well plate format and validated its application in a cell viability HTS assay by screening a 2036-compound library.We further miniaturized the 3D organoid culturing in a 1536-well ultra-HTS format and demonstrated its robust performance for large-scale primary compound screening.Our miniaturized organoid culturing method may be adapted to other types of organoids.By leveraging the power of 3D organoid culture in a high-density plate format,we provide a physiologically relevant screening platform to model tumors to accelerate organoid-based research and drug discovery. | Yuhong Du Xingnan Li Qiankun Niu Xiulei Mo Min Qui Tingxuan Ma Calvin J.Kuo Haian Fu | 2020 | Journal of Molecular Cell Biology2020，12，8： | 1 |
| 8 | 14-3-3 Proteins Mediate an Essential Antiapoptotie Signal显示文摘 | Shane C M Haian Fu | 2001 | J Biol Chem2001，276，45： | 1 |
| 9 | TMPRSS2 and SARS-CoV-2 SPIKE interaction assay for uHTS显示文摘SARS-CoV-2,the coronavirus that causes the disease COVID-19,has claimed millions of lives over the past 2 years.This demands rapid development of effective therapeutic agents that target various phases of the viral replication cycle.The interaction between host transmembrane serine protease 2(TMPRSS2)and viral SPIKE protein is an important initial step in SARS-CoV-2 infection,offering an opportunity for therapeutic development of viral entry inhibitors.Here,we report the development of a time-resolved fluorescence/Förster resonance energy transfer(TR-FRET)assay for monitoring the TMPRSS2–SPIKE interaction in lysate from cells co-expressing these proteins.The assay was configured in a 384-well-plate format for high-throughput screening with robust assay performance.To enable large-scale compound screening,we further miniaturized the assay into 1536-well ultrahigh-throughput screening(uHTS)format.A pilot screen demonstrated the utilization of the assay for uHTS.Our optimized TR-FRET uHTS assay provides an enabling platform for expanded screening campaigns to discover new classes of small-molecule inhibitors that target the SPIKE and TMPRSS2 protein–protein interaction. | Danielle Cicka Qiankun Niu Min Qui Kun Qian Eric Miller Dacheng Fan Xiulei Mo Andrey AIvanov Stefan GSarafianos Yuhong Du Haian Fu | 2023 | Journal of Molecular Cell Biology2023，15，3： | 0 |
| 10 | 鉴定新的14-3-3结合蛋白HIP-55负调控HPK1激酶活性显示文摘 | 李子健 张幼怡 Haian Fu | 2010 | 中国病理生理杂志2010，26，A10： | 0 |
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