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Srikanth Appikonda, Kaushik N Thakkar, Parantu K Shah, Sharon Y R Dent, Jannik N Andersen, Michelle Craig Barton
Proteins with domains that recognize and bind post-translational modifications (PTMs) of histones are collectively termed epigenetic readers. Numerous interactions between specific reader protein domains and histone PTMs and their regulatory outcomes have been reported, but little is known about how reader proteins may in turn be modulated by these interactions. Tripartite motif-containing protein 24 (TRIM24) is a histone reader aberrantly expressed in multiple cancers. Here, our investigation revealed functional crosstalk between histone acetylation and TRIM24 SUMOylation...
March 9, 2018: Journal of Biological Chemistry
Lara N Gechijian, Dennis L Buckley, Matthew A Lawlor, Jaime M Reyes, Joshiawa Paulk, Christopher J Ott, Georg E Winter, Michael A Erb, Thomas G Scott, Mousheng Xu, Hyuk-Soo Seo, Sirano Dhe-Paganon, Nicholas P Kwiatkowski, Jennifer A Perry, Jun Qi, Nathanael S Gray, James E Bradner
The addressable pocket of a protein is often not functionally relevant in disease. This is true for the multidomain, bromodomain-containing transcriptional regulator TRIM24. TRIM24 has been posited as a dependency in numerous cancers, yet potent and selective ligands for the TRIM24 bromodomain do not exert effective anti-proliferative responses. We therefore repositioned these probes as targeting features for heterobifunctional protein degraders. Recruitment of the VHL E3 ubiquitin ligase by dTRIM24 elicits potent and selective degradation of TRIM24...
March 5, 2018: Nature Chemical Biology
Liangqin Shi, Chao Huang, Qihui Luo, Yu Xia, Heng Liu, Like Li, Wentao Liu, Wenjing Ma, Jing Fang, Li Tang, Wen Zeng, Zhengli Chen
Clinical diagnosis of Parkinson's disease (PD) is characterized by the classical features of tremor, bradykinesia and rigidity, which are present only when more than 70%-80% degeneration of dopaminergic (DA) neurons in the substantia nigra. The lack of means for early diagnosis of PD has elicited interest in searching for its risk factors, which, by now, are almost obtained at a single time point in PD process, and little developing risk factors, obtained from completely normal situation to the onset or even advanced stage of PD in individual person which could monitor the progress of PD, are present...
December 1, 2017: Oncotarget
Valeria Tomati, Emanuela Pesce, Emanuela Caci, Elvira Sondo, Paolo Scudieri, Monica Marini, Felice Amato, Giuseppe Castaldo, Roberto Ravazzolo, Luis J V Galietta, Nicoletta Pedemonte
In cystic fibrosis, deletion of phenylalanine 508 (F508del) in the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel causes misfolding and premature degradation. One possible approach to reducing the detrimental health effects of cystic fibrosis could be the identification of proteins whose suppression rescues F508del-CFTR function in bronchial epithelial cells. However, searches for these potential targets have not yet been conducted, particularly in a relevant airway background using a functional readout...
January 26, 2018: Journal of Biological Chemistry
Deguan Lv, Yanxin Li, Weiwei Zhang, Angel A Alvarez, Lina Song, Jianming Tang, Wei-Qiang Gao, Bo Hu, Shi-Yuan Cheng, Haizhong Feng
Aberrant amplification and mutations of epidermal growth factor receptor (EGFR) are the most common oncogenic events in glioblastoma (GBM), but the mechanisms by which they promote aggressive pathogenesis are not well understood. Here, we determine that non-canonical histone signature acetylated H3 lysine 23 (H3K23ac)-binding protein tripartite motif-containing 24 (TRIM24) is upregulated in clinical GBM specimens and required for EGFR-driven tumorigenesis. In multiple glioma cell lines and patient-derived glioma stem cells (GSCs), EGFR signaling promotes H3K23 acetylation and association with TRIM24...
November 13, 2017: Nature Communications
Yuichiro Kanno, Yuki Kure, Saori Kobayashi, Mariko Mizuno, Yumi Tsuchiya, Naoya Yamashita, Kiyomitsu Nemoto, Yoshio Inouye
The constitutive active/androstane receptor (CAR) is a nuclear receptor that acts as a transcription factor for a variety of genes, including genes encoding xenobiotic, steroid and drug-metabolizing enzymes and transporters. Transactivation of a target gene by a transcription factor is generally mediated through the concerted and stepwise recruitment of various proteins termed co-regulators, including coactivators and corepressors. In this study, tripartite motif containing 24 (TRIM24; also known as transcriptional intermediary factor 1 alpha) was found to interact with the CAR...
November 3, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Deguan Lv, Feng Jia, Yanli Hou, Youzhou Sang, Angel A Alvarez, Weiwei Zhang, Wei-Qiang Gao, Bo Hu, Shi-Yuan Cheng, Jianwei Ge, Yanxin Li, Haizhong Feng
Lysine acetyltransferase KAT6A is a chromatin regulator that contributes to histone modification and cancer, but the basis of its actions are not well understood. Here, we identify a KAT6A signaling pathway that facilitates glioblastoma (GBM), where it is upregulated. KAT6A expression was associated with GBM patient survival. KAT6A silencing suppressed cell proliferation, cell migration, colony formation, and tumor development in an orthotopic mouse xenograft model system. Mechanistic investigations demonstrated that KAT6A acetylates lysine 23 of histone H3 (H3K23), which recruits the nuclear receptor binding protein TRIM24 to activate PIK3CA transcription, thereby enhancing PI3K/AKT signaling and tumorigenesis...
November 15, 2017: Cancer Research
Feng-Qin Wang, Yan Han, WenJuan Yao, Jing Yu
Colorectal cancer is one of the most frequent malignancies in the world. Tripartite motif containing 24 (TRIM24) is a member of the TRIM protein family and a coregulator for multiple nuclear receptors. Altered expression of TRIM24 has been shown in a spectrum of human cancers. However, the clinical role of TRIM24 in colorectal cancer remains unknown. Here, gene expression data in colorectal cancer and normal tissues were downloaded from Gene Expression Omnibus (GEO). Western blotting analysis was conducted to compare TRIM24 expression between colorectal cancer and non-cancerous tissues...
October 2017: Pathology, Research and Practice
Ankush Borlepawar, Ashraf Yusuf Rangrez, Alexander Bernt, Lynn Christen, Samuel Sossalla, Derk Frank, Norbert Frey
We have previously shown that dysbindin is a potent inducer of cardiomyocyte hypertrophy via activation of Rho-dependent serum-response factor (SRF) signaling. We have now performed a yeast two-hybrid screen using dysbindin as bait against a cardiac cDNA library to identify the cardiac dysbindin interactome. Among several putative binding proteins, we identified tripartite motif-containing protein 24 (TRIM24) and confirmed this interaction by co-immunoprecipitation and co-immunostaining. Another tripartite motif (TRIM) family protein, TRIM32, has been reported earlier as an E3 ubiquitin ligase for dysbindin in skeletal muscle...
June 16, 2017: Journal of Biological Chemistry
Ziling Fang, Jun Deng, Ling Zhang, Xiaojun Xiang, Feng Yu, Jun Chen, Miao Feng, Jianping Xiong
Tripartite motif-containing 24 (TRIM24) is important in tumor development and progression. However, the role of TRIM24 in gastric cancer (GC) and the mechanisms underlying the dysregulated expression of TRIM24 remain to be fully elucidated. In the present study, it was found that TRIM24 was frequently overexpressed in GC cell lines and tissues compared with normal controls, as determined by western blotting and immunohistochemical staining. The high nuclear expression of TRIM24 was correlated with the depth of invasion (P=0...
March 2017: Oncology Letters
Gianluca Mazzoni, Suraya M Salleh, Kristine Freude, Hanne S Pedersen, Lotte Stroebech, Henrik Callesen, Poul Hyttel, Haja N Kadarmideen
The Ovum Pick Up-In vitro Production (OPU-IVP) of embryos is an advanced reproductive technology used in cattle production but the complex biological mechanisms behind IVP outcomes are not fully understood. In this study we sequenced RNA of granulosa cells collected from Holstein cows at oocyte aspiration prior to IVP, to identify candidate genes and biological mechanisms for favourable IVP-related traits in donor cows where IVP was performed separately for each animal. We identified 56 genes significantly associated with IVP scores (BL rate, kinetic and morphology)...
2017: PloS One
Maisa Pinheiro, Sandra Aparecida Drigo, Renata Tonhosolo, Sonia C S Andrade, Fabio Albuquerque Marchi, Igor Jurisica, Luiz Paulo Kowalski, Maria Isabel Achatz, Silvia Regina Rogatto
Familial Papillary Thyroid Carcinoma (PTC) has been described as a hereditary predisposition cancer syndrome associated with mutations in candidate genes including HABP2. Two of 20 probands from families with history of PTC and breast carcinoma (BC) were evaluated by whole exome sequencing (WES) revealing HABP2 p.G534E. Sanger sequencing was used to confirm the involvement of this variant in three families (F1: 7 relatives; F2: 3 and F3: 3). The proband and his sister (with no malignant tumor so far) from F1 were homozygous for the variant whereas one relative with PTC from F2 was negative for the variant...
June 20, 2017: Oncotarget
Li Lin, Weihua Zhao, Bo Sun, Xinyu Wang, Qiao Liu
TRIM24, originally known as intermediary factor 1-alpha, is involved in the development of several cancers. This study aimed to evaluate the expression level and prognostic value of TRIM24 in cervical cancer. In the present study, we showed that the expression of TRIM24 was markedly upregulated in cervical cancer cell lines and cancerous specimens at both transcriptional and translational levels. TRIM24 expression was analyzed in 147 archived cervical cancer specimens using immunohistochemistry, and the correlation between TRIM24 expression and clinicopathological parameters was evaluated...
2017: American Journal of Translational Research
Jiuyang Liu, Fudong Li, Hongyu Bao, Yiyang Jiang, Shuya Zhang, Rongsheng Ma, Jia Gao, Jihui Wu, Ke Ruan
Tripartite motif-containing protein 24 (TRIM24) is closely correlated with multiple cancers, and a recent study demonstrated that the bromodomain of TRIM24 is essential for the proliferation of lethal castration-resistant prostate cancer. Here, we identify three new inhibitors of the TRIM24 bromodomain using NMR fragment-based screening. The crystal structures of two new inhibitors in complex with the TRIM24 bromodomain reveal that the water-bridged interaction network is conserved in the same fashion as those for known benzoimidazolone inhibitors...
April 2017: FEBS Journal
Ziling Fang, Ling Zhang, Quan Liao, Yi Wang, Feng Yu, Miao Feng, Xiaojun Xiang, Jianping Xiong
BACKGROUND: Increasing evidence highlights the important roles of tripartite motif containing 24 (TRIM24) in tumor initiation and malignant progression in many tumors, including gastric cancer (GC). Although TRIM24 expression is remarkably upregulated during GC carcinogenesis, the molecular mechanisms underlying TRIM24 dysregulation remain unexplored. METHODS: In this study, miRNA target prediction tools were applied to explore miRNAs that potentially target TRIM24...
January 23, 2017: Journal of Experimental & Clinical Cancer Research: CR
Sheng-Lin Zhu, Xi Chen, Liang-Jie Wang, Wei-Wei Wan, Qi-Lin Xin, Wei Wang, Gengfu Xiao, Lei-Ke Zhang
Sendai virus (SeV) is an enveloped nonsegmented negative-strand RNA virus that belongs to the genus Respirovirus of the Paramyxoviridae family. As a model pathogen, SeV has been extensively studied to define the basic biochemical and molecular biologic properties of the paramyxoviruses. In addition, SeV-infected host cells were widely employed to uncover the mechanism of innate immune response. To identify proteins involved in the SeV infection process or the SeV-induced innate immune response process, system-wide evaluations of SeV-host interactions have been performed...
March 2017: Proteomics
Yu-Chan Chang, Li-Hsing Chi, Wei-Ming Chang, Chia-Yi Su, Yuang-Feng Lin, Chi-Long Chen, Ming-Huang Chen, Peter Mu-Hsin Chang, Alex T H Wu, Michael Hsiao
BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) represents a unique and major health concern worldwide. Significant increases in glucose uptake and aerobic glycolysis have been observed in HNSCC cells. Glucose transporters (GLUTs) represent a major hub in the glycolysis pathway, with GLUT4 having the highest glucose affinity. However, GLUT4's role in HNSCC has not been fully appreciated. METHODS: An in silico analysis was performed in HNSCC cohorts to identify the most significant glucose transporter associated with HNSCC patient prognosis...
January 7, 2017: Journal of Hematology & Oncology
Shengjiang Tu, Gary LeRoy, Danny Reinberg
In an effort to identify a chromatin-associated pluripotent network, Rafiee et al., (2016) developed a powerful ChIP-MS technique and discovered a novel protein, TRIM24, enriched on OCT4-, SOX2-, and NANOG-associated chromatin, paving the way for future proteomic studies on chromatin.
November 3, 2016: Molecular Cell
V V Nenasheva, E V Novosadova, I V Makarova, O S Lebedeva, M A Grefenshtein, E L Arsenyeva, S A Antonov, I A Grivennikov, V Z Tarantul
Over the last few years, in vitro models, based on patient-derived induced pluripotent stem cells (iPSCs), have received considerable attention for modeling different neurodegenerative disorders. Using this model, we analyzed transcription of 15 tripartite motif (trim) genes in iPSCs, derived from the different groups: Parkinson's disease (PD) patients bearing mutations in different genes, patient with the sporadic form of PD, and the healthy individuals. The transcription was observed during neuronal differentiation of the cells in vitro into neuronal stem cells and terminally differentiated neurons...
October 29, 2016: Molecular Neurobiology
Mahmoud-Reza Rafiee, Charles Girardot, Gianluca Sigismondo, Jeroen Krijgsveld
Maintenance of pluripotency is regulated by a network of transcription factors coordinated by Oct4, Sox2, and Nanog (OSN), yet a systematic investigation of the composition and dynamics of the OSN protein network specifically on chromatin is still missing. Here we have developed a method combining ChIP with selective isolation of chromatin-associated proteins (SICAP) followed by mass spectrometry to identify chromatin-bound partners of a protein of interest. ChIP-SICAP in mouse embryonic stem cells (ESCs) identified over 400 proteins associating with OSN, including several whose interaction depends on the pluripotent state...
November 3, 2016: Molecular Cell
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