更新于：2024-11-01

RARα x SIN3A

更新于：2024-11-01

基本信息

关联

项与 RARα x SIN3A 相关的药物

C16-AM-80

靶点

RARα x SIN3A

作用机制

RARα激动剂 [+1]

在研机构

Mount Sinai Medical Center of Florida, Inc. [+1]

原研机构

Mount Sinai Medical Center of Florida, Inc.

在研适应症

肿瘤

非在研适应症-

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

100 项与 RARα x SIN3A 相关的临床结果

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100 项与 RARα x SIN3A 相关的转化医学

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0 项与 RARα x SIN3A 相关的专利（医药）

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项与 RARα x SIN3A 相关的文献（医药）

2022-01-01·Archives of Biochemistry and Biophysics3区 · 生物学

Systems biomarkers for papillary thyroid cancer prognosis and treatment through multi-omics networks

3区 · 生物学

Article

作者: Erdonmez, Habib Burak Can ; Arga, Kazim Yalcin ; Gulfidan, Gizem ; Demirel, Damla ; Turanli, Beste ; Soylu, Melisa ; Ozbek Sarica, Pemra ; Beklen, Hande

The identification of biomolecules associated with papillary thyroid cancer (PTC) has upmost importance for the elucidation of the disease mechanism and the development of effective diagnostic and treatment strategies. Despite particular findings in this regard, a holistic analysis encompassing molecular data from different biological levels has been lacking. In the present study, a meta-analysis of four transcriptome datasets was performed to identify gene expression signatures in PTC, and reporter molecules were determined by mapping gene expression data onto three major cellular networks, i.e., transcriptional regulatory, protein-protein interaction, and metabolic networks. We identified 282 common genes that were differentially expressed in all PTC datasets. In addition, six proteins (FYN, JUN, LYN, PML, SIN3A, and RARA), two Erb-B2 receptors (ERBB2 and ERBB4), two cyclin-dependent receptors (CDK1 and CDK2), and three histone deacetylase receptors (HDAC1, HDAC2, and HDAC3) came into prominence as proteomic signatures in addition to several metabolites including lactaldehyde and proline at the metabolome level. Significant associations with calcium and MAPK signaling pathways and transcriptional and post-transcriptional activities of 12 TFs and 110 miRNAs were also observed at the regulatory level. Among them, six miRNAs (miR-30b-3p, miR-15b-5p, let-7a-5p, miR-130b-3p, miR-424-5p, and miR-193b-3p) were associated with PTC for the first time in the literature, and the expression levels of miR-30b-3p, miR-15b-5p, and let-7a-5p were found to be predictive of disease prognosis. Drug repositioning and molecular docking simulations revealed that 5 drugs (prochlorperazine, meclizine, rottlerin, cephaeline, and tretinoin) may be useful in the treatment of PTC. Consequently, we report here biomolecule candidates that may be considered as prognostic biomarkers or potential therapeutic targets for further experimental and clinical trials for PTC.

2006-07-01·Molecular and Cellular Biology3区 · 生物学

Btg2 Enhances Retinoic Acid-Induced Differentiation by Modulating Histone H4 Methylation and Acetylation

3区 · 生物学

Article

作者: Rizzo, Giovanni ; Passeri, Daniela ; Leonardi, Luca ; Tirone, Felice ; Marcucci, Antonella ; Panigada, Maddalena ; Grignani, Francesco ; Billi, Monia

ABSTRACT Retinoic acid controls hematopoietic differentiation through the transcription factor activity of its receptors. They act on specific target genes by recruiting protein complexes that deacetylate or acetylate histones and modify chromatin status. The regulation of this process is affected by histone methyltransferases, which can inhibit or activate transcription depending on their amino acid target. We show here that retinoic acid treatment of hematopoietic cells induces the expression of BTG2. Overexpression of this protein increases RARα transcriptional activity and the differentiation response to retinoic acid of myeloid leukemia cells and CD34 + hematopoietic progenitors. In the absence of retinoic acid, BTG2 is present in the RARα transcriptional complex, together with the arginine methyltransferase PRMT1 and Sin3A. Overexpressed BTG2 increases PRMT1 participation in the RARα protein complex on the RARβ promoter, a target gene model, and enhances gene-specific histone H4 arginine methylation. Upon RA treatment Sin3A, BTG2, and PRMT1 detach from RARα and thereafter BGT2 and PRMT1 are driven to the cytoplasm. These events prime histone H4 demethylation and acetylation. Overall, our data show that BTG2 contributes to retinoic acid activity by favoring differentiation through a gene-specific modification of histone H4 arginine methylation and acetylation levels.

2000-03-01·Molecular and Cellular Biology3区 · 生物学

The ETO Protein Disrupted in t(8;21)-Associated Acute Myeloid Leukemia Is a Corepressor for the Promyelocytic Leukemia Zinc Finger Protein

3区 · 生物学

Article

作者: Ball, Helen J. ; Licht, Jonathan D. ; Hiebert, Scott W. ; Lutterbach, Bart ; Arai, Sally ; Carlile, Graeme W. ; Polinger, Adam ; Westendorf, Jennifer J. ; Melnick, Ari M.

ABSTRACTThe ETO protein was originally identified by its fusion to the AML-1 transcription factor in translocation (8;21) associated with the M2 form of acute myeloid leukemia (AML). The resulting AML-1–ETO fusion is an aberrant transcriptional regulator due to the ability of ETO, which does not bind DNA itself, to recruit the transcriptional corepressors N-CoR, SMRT, and Sin3A and histone deacetylases. The promyelocytic leukemia zinc finger (PLZF) protein is a sequence-specific DNA-binding transcriptional factor fused to retinoic acid receptor α in acute promyelocytic leukemia associated with the (11;17)(q23;q21) translocation. PLZF also mediates transcriptional repression through the actions of corepressors and histone deacetylases. We found that ETO is one of the corepressors recruited by PLZF. The PLZF and ETO proteins associate in vivo and in vitro, and ETO can potentiate transcriptional repression by PLZF. The N-terminal portion of ETO forms complexes with PLZF, while the C-terminal region, which was shown to bind to N-CoR and SMRT, is required for the ability of ETO to augment transcriptional repression by PLZF. The second repression domain (RD2) of PLZF, not the POZ/BTB domain, is necessary to bind to ETO. Corepression by ETO was completely abrogated by histone deacetylase inhibitors. This identifies ETO as a cofactor for a sequence-specific transcription factor and indicates that, like other corepressors, it functions through the action of histone deactylase.