keyword
MENU ▼
Read by QxMD icon Read
search

Lysine specific demethylase

keyword
https://www.readbyqxmd.com/read/28088469/estrogen-induced-expression-of-tissue-factor-pathway-inhibitor-2-in-mcf7-cells-involves-lysine-specific-demethylase-1
#1
Marianne S Andresen, Huda Omar Ali, Christiane Filion Myklebust, Per Morten Sandset, Benedicte Stavik, Nina Iversen, Grethe Skretting
Hormone-sensitive cancers can be influenced by estrogens, a process usually mediated through the estrogen receptor (ER). Tissue factor pathway inhibitor type 2 (TFPI-2) is a Kunitz-type serine protease inhibitor involved in regulating the extracellular matrix. The present study demonstrates that the expression of TFPI-2 can be induced by estrogens. Breast cancer data from GOBO displayed increased levels of TFPI-2 and increased survival in patients with ERα+ tumors. Treatment of MCF7 cells (ERα+) with 17β-estradiol (E2) or 17α-ethinyl estradiol (EE2) increased TFPI-2 mRNA and protein levels...
January 11, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28069602/oncogenic-zeb2-activation-drives-sensitivity-towards-kdm1a-inhibition-in-t-cell-acute-lymphoblastic-leukemia
#2
Steven Goossens, Sofie Peirs, Wouter Van Loocke, Jueqiong Wang, Mina Takawy, Filip Matthijssens, Stefan E Sonderegger, Katharina Haigh, Thao Nguyen, Niels Vandamme, Magdaline Costa, Catherine Carmichael, Filip Van Nieuwerburgh, Dieter Deforce, Oded Kleifeld, David J Curtis, Geert Berx, Pieter Van Vlierberghe, Jody J Haigh
Elevated expression of the Zinc finger E-box binding homeobox transcription factor-2 (ZEB2) is correlated with poor prognosis and patient outcome in a variety of human cancer subtypes. Using a conditional gain-of-function mouse model, we recently demonstrated that ZEB2 is an oncogenic driver of immature T-cell acute lymphoblastic leukemia (T-ALL), a heterogenic subgroup of human leukemia characterized by a high incidence of remission failure or hematological relapse after conventional chemotherapy. Here, we identified the Lysine-specific demethylase KDM1A as a novel interaction partner of ZEB2 and demonstrated that mouse and human T-ALLs with increased ZEB2 levels critically depend on KDM1A activity for survival...
January 9, 2017: Blood
https://www.readbyqxmd.com/read/28065500/activation-of-lysine-specific-demethylase-1-inhibitor-peptide-by-redox-controlled-cleavage-of-a-traceless-linker
#3
Yuichi Amano, Naoki Umezawa, Shin Sato, Hisami Watanabe, Takashi Umehara, Tsunehiko Higuchi
We have previously employed cyclization of a linear peptide as a strategy to modulate peptide function and properties, but cleavage to regenerate the linear peptide left parts of the linker structure on the peptide, interfering with its activity. Here, we focused on cyclization of a linear peptide via a "traceless" disulfide-based linkage that would be cleaved and completely removed in a reducing environment, regenerating the original linear peptide without any linker-related structure. Thus, the linker would serve as a redox switch that would be activated in the intracellular environment...
December 23, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28049654/histone-lysine-demethylase-inhibitors
#4
REVIEW
Ashwini Jambhekar, Jamie N Anastas, Yang Shi
The dynamic regulation of covalent modifications to histones is essential for maintaining genomic integrity and cell identity and is often compromised in cancer. Aberrant expression of histone lysine demethylases has been documented in many types of blood and solid tumors, and thus demethylases represent promising therapeutic targets. Recent advances in high-throughput chemical screening, structure-based drug design, and structure-activity relationship studies have improved both the specificity and the in vivo efficacy of demethylase inhibitors...
January 3, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28041878/epigenetic-modifiers-facilitate-induction-and-pluripotency-of-porcine-ipscs
#5
Jian Mao, Qian Zhang, Wei Deng, Hua Wang, Kai Liu, Haifeng Fu, Qiang Zhao, Xumin Wang, Lin Liu
Inadequate silencing of exogenous genes represents a major obstacle to complete epigenetic reprogramming of porcine-induced pluripotent stem cells (piPSCs) by conventional pluripotency transcription factors (OSKM). We tested the hypothesis that epigenetic modification by active DNA or histone demethylation or by inhibition of histone deacetylase would enhance reprogramming and exogenous gene silencing in piPSCs. piPSCs induced by OSKM in combination with epigenetic factors, specifically Ten-Eleven Translocation (Tet1 or Tet3) or lysine (K)-specific demethylase 3A (Kdm3a), expressed higher levels of Rex1 and other genes representing naive state and exhibited more open chromatin status, compared with those of OSKM controls...
January 10, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28029651/the-pseudogene-duxap10-promotes-an-aggressive-phenotype-through-binding-with-lsd1-and-repressing-lats2-and-rrad-in-non-small-cell-lung-cancer
#6
Chen-Chen Wei, Feng-Qi Nie, Li-Li Jiang, Qin-Nan Chen, Zhen-Yao Chen, Xin Chen, Xuan Pan, Zhi-Li Liu, Bin-Bin Lu, Zhao-Xia Wang
Pseudogenes have been considered as non-functional transcriptional relics of human genomic for long time. However, recent studies revealed that they play a plethora of roles in diverse physiological and pathological processes, especially in cancer, and many pseudogenes are transcribed into long noncoding RNAs and emerging as a novel class of lncRNAs. However, the biological roles and underlying mechanism of pseudogenes in the pathogenesis of non small cell lung cancer are still incompletely elucidated. This study identifies a putative oncogenic pseudogene DUXAP10 in NSCLC, which is located in 14q11...
December 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27994610/genome-wide-analysis-of-soybean-jmjc-domain-containing-proteins-suggests-evolutionary-conservation-following-whole-genome-duplication
#7
Yapeng Han, Xiangyong Li, Lin Cheng, Yanchun Liu, Hui Wang, Danxia Ke, Hongyu Yuan, Liangsheng Zhang, Lei Wang
Histone modifications, such as methylation and demethylation, play an important role in regulating chromatin structure and gene expression. The JmjC domain-containing proteins, an important family of histone lysine demethylases (KDMs), play a key role in maintaining homeostasis of histone methylation in vivo. In this study, we performed a comprehensive analysis of the jumonji C (JmjC) gene family in the soybean genome and identified 48 JmjC genes (GmJMJs) distributed unevenly across 18 chromosomes. Phylogenetic analysis showed that these JmjC domain-containing genes can be divided into eight groups...
2016: Frontiers in Plant Science
https://www.readbyqxmd.com/read/27989416/towards-the-development-of-activity-based-probes-for-detection-of-lysine-specific-demethylase-1-activity
#8
Maria E Ourailidou, Alessia Lenoci, Clemens Zwergel, Dante Rotili, Antonello Mai, Frank J Dekker
The implications of lysine-specific demethylase-1 (LSD1) in tumorigenesis have urged scientists to develop diagnostic tools in order to explore the function of this enzyme. In this work, we present our efforts on the development of tranylcypromine (TCP)-based functionalized probes for activity-based protein profiling (ABPP) of LSD1 activity. Biotinylated forms of selected compounds enabled dose-dependent enzyme labeling of recombinant LSD1. However, treatment with LSD1 inhibitors did not clearly reduce the LSD1 labeling efficiency thus indicating that labeling using these probes is not activity dependent...
December 1, 2016: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/27986293/neurolsd1-splicing-generated-epigenetic-enhancer-of-neuroplasticity
#9
REVIEW
Francesco Rusconi, Barbara Grillo, Emanuela Toffolo, Andrea Mattevi, Elena Battaglioli
The acquisition and maintenance of the specific neuronal functions underlying learning, memory, and emotion require transduction of environmental stimuli into remodeling of neuronal circuitry. This process occurs via induction of plasticity-related transcriptional programs. The epigenetic enzyme lysine-specific demethylase-1 (LSD1), also known as lysine demethylase 1A (KDM1A), and its neurospecific splicing variant neuroLSD1 have been implicated in this process through an antagonistic mechanism. Specifically, LSD1/neuroLSD1 are involved in the negative and positive regulation of activity-evoked transcription of immediate early genes (IEGs) impacting memory formation and emotional behavior...
January 2017: Trends in Neurosciences
https://www.readbyqxmd.com/read/27977115/lsd1-substrate-binding-and-gene-expression-are-affected-by-hdac1-mediated-deacetylation
#10
Dhanusha A Nalawansha, Mary Kay H Pflum
Lysine Specific Demethylase 1 (LSD1) catalyzes the demethylation of histone 3 to regulate gene expression. With a fundamental role in gene regulation, LSD1 is involved in multiple cellular processes, including embryonic development, cell proliferation, and metastasis. Significantly, LSD1 is overexpressed in multiple cancers and has emerged as a potential anticancer drug target. LSD1 is typically found in association with another epigenetic enzyme, histone deacetylase (HDAC). HDAC and LSD1 inhibitor compounds have been tested as combination anticancer agents...
December 15, 2016: ACS Chemical Biology
https://www.readbyqxmd.com/read/27914215/lysine-specific-demethylase-1-lsd1-inhibitor-s2101-induces-autophagy-via-the-akt-mtor-pathway-in-skov3-ovarian-cancer-cells
#11
Shujun Feng, Ye Jin, Mengjiao Cui, Jianhua Zheng
BACKGROUND S2101 is one of the most potent LSD1 inhibitors, which can inhibit ovarian cancer cells viability. This study aimed to detect the mechanism behind the anticancer properties of S2101 in SKOV3 ovarian cells. MATERIAL AND METHODS Cell viability was tested by Cell Counting Kit-8 (CCK-8) assay. Cellular apoptosis and autophagy were evaluated by flow cytometric analysis using Annexin-V/PI staining methods and Green fluorescent protein (GFP)-fused-LC3 (GFP-LC3), respectively. Western blotting was performed for analyzing the Bax, Bcl-2, mTOR, p- mTOR, p62, LC3-I, LC3-II, AKT, and p-AKT protein expression...
December 3, 2016: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/27910233/a-genetically-encoded-allysine-for-the-synthesis-of-proteins-with-site-specific-lysine-dimethylation
#12
Zhipeng A Wang, Yu Zeng, Yadagiri Kurra, Xin Wang, Jeffery M Tharp, Erol C Vatansever, Willie W Hsu, Susie Dai, Xinqiang Fang, Wenshe R Liu
Using the amber suppression approach, N(ϵ) -(4-azidobenzoxycarbonyl)-δ,ϵ-dehydrolysine, an allysine precursor is genetically encoded in E. coli. Its genetic incorporation followed by two sequential biocompatible reactions allows convenient synthesis of proteins with site-specific lysine dimethylation. Using this approach, dimethyl-histone H3 and p53 proteins have been synthesized and used to probe functions of epigenetic enzymes including histone demethylase LSD1 and histone acetyltransferase Tip60. We confirmed that LSD1 is catalytically active toward H3K4me2 and H3K9me2 but inert toward H3K36me2, and methylation at p53 K372 directly activates Tip60 for its catalyzed acetylation at p53 K120...
January 2, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27900345/new-insight-into-lsd1-function-in-human-cortical-neurogenesis
#13
Kazumi Hirano, Masakazu Namihira
The cerebral cortex of primates has evolved massively and intricately in comparison to that of other species. Accumulating evidence indicates that this is caused by changes in cell biological features of neural stem cells (NSCs), which differentiate into neurons and glial cells during development. The fate of NSCs during rodent cortical development is stringently regulated by epigenetic factors, such as histone modification enzymes, but the role of these factors in human corticogenesis is largely unknown. We have recently discovered that a lysine-specific demethylase 1 (LSD1), which catalyzes the demethylation of methyl groups in the histone tail, plays a unique role in human fetal NSCs (hfNSCs)...
2016: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/27894088/lsd1-binds-to-hpv16-e7-and-promotes-the-epithelial-mesenchymal-transition-in-cervical-cancer-by-demethylating-histones-at-the-vimentin-promoter
#14
Yuan Liu, Yanan Wang, Chunqin Chen, Jiawen Zhang, Wenyan Qian, Yu Dong, Zhiqiang Liu, Xi Zhang, Xiaoyun Wang, Zhenbo Zhang, Xiaobing Shi, Sufang Wu
Lysine-specific demethylase 1 (LSD1), which specifically demethylates histone H3 lysine 4 (H3K4) and lysine 9 (H3K9), is dysregulated in several cancers. We found that ectopic expression of LSD1 in cervical cancer cells promoted invasion and metastasis in vitro and in vivo, reduced the expression of the epithelial marker E-cadherin, and induced the expression of the mesenchymal marker, Vimentin. By contrast, LSD1 knockdown had the opposite effect and attenuated the HPV16 E7-induced epithelial-mesenchymal transition (EMT)...
November 23, 2016: Oncotarget
https://www.readbyqxmd.com/read/27894074/lsd1-mediates-mycn-control-of-epithelial-mesenchymal-transition-through-silencing-of-metastatic-suppressor-ndrg1-gene
#15
Susanna Ambrosio, Stefano Amente, Carmen D Saccà, Mario Capasso, Raffaele A Calogero, Luigi Lania, Barbara Majello
Neuroblastoma (NB) with MYCN amplification is a highly aggressive and metastatic tumor in children. The high recurrence rate and resistance of NB cells to drugs urgently demands a better therapy for this disease. We have recently found that MYCN interacts with the lysine-specific demethylase 1 (LSD1), a histone modifier that participates in key aspects of gene transcription. In cancer cells, LSD1 contributes to the genetic reprogramming that underlies to Epithelial-Mesenchymal Transition (EMT) and tumor metastasis...
November 22, 2016: Oncotarget
https://www.readbyqxmd.com/read/27893888/potential-neuroprotective-effects-of-an-lsd1-inhibitor-in-retinal-ganglion-cells-via-p38-mapk-activity
#16
Takayuki Tsutsumi, Keiichiro Iwao, Hideki Hayashi, Tomoko Kirihara, Takahiro Kawaji, Toshihiro Inoue, Shinjiro Hino, Mitsuyoshi Nakao, Hidenobu Tanihara
Purpose: The epigenetic mechanisms associated with ocular neurodegenerative diseases remain unclear. The present study aimed to determine the role of lysine-specific demethylase 1 (LSD1), which represses transcription by removing the methyl group from methylated lysine 4 of histone H3, in retinal ganglion cell (RGC) survival, and to investigate the details of the neuroprotective mechanism of tranylcypromine, a major LSD1 inhibitor. Methods: The authors evaluated whether tranylcypromine contributes to neuronal survival following stress-induced damage using primary cultured rat RGCs and in vivo N-methyl-D-aspartate (NMDA)-induced excitotoxicity...
November 1, 2016: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/27893719/novel-kdm1a-inhibitors-induce-differentiation-and-apoptosis-of-glioma-stem-cells-via-unfolded-protein-response-pathway
#17
G R Sareddy, S Viswanadhapalli, P Surapaneni, T Suzuki, A Brenner, R K Vadlamudi
Glioma stem cells (GSCs) have a central role in glioblastoma (GBM) development and chemo/radiation resistance, and their elimination is critical for the development of efficient therapeutic strategies. Recently, we showed that lysine demethylase KDM1A is overexpressed in GBM. In the present study, we determined whether KDM1A modulates GSCs stemness and differentiation and tested the utility of two novel KDM1A-specific inhibitors (NCL-1 and NCD-38) to promote differentiation and apoptosis of GSCs. The efficacy of KDM1A targeting drugs was tested on purified GSCs isolated from established and patient-derived GBMs using both in vitro assays and in vivo orthotopic preclinical models...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27893717/androgen-and-ar-contribute-to-breast-cancer-development-and-metastasis-an-insight-of-mechanisms
#18
J Feng, L Li, N Zhang, J Liu, L Zhang, H Gao, G Wang, Y Li, Y Zhang, X Li, D Liu, J Lu, B Huang
The role of androgen and androgen receptor (AR) in breast carcinogenesis has long been a disputed issue. This report provides a mechanistic insight into how androgen and AR contributes to invasion and metastasis of breast cancer. We find that dihydrotestosterone (DHT) is able to induce the epithelial-to-mesenchymal transition in breast cancer cells in an AR-dependent/estrogen receptor-independent manner. This process is dependent on the demethylation activity of lysine-specific demethylase 1A (LSD1) by epigenetically regulating the target genes E-cadherin and vimentin...
November 28, 2016: Oncogene
https://www.readbyqxmd.com/read/27888721/discovery-of-resveratrol-derivatives-as-novel-lsd1-inhibitors-design-synthesis-and-their-biological-evaluation
#19
Ying-Chao Duan, Yuan-Yuan Guan, Xiao-Yu Zhai, Li-Na Ding, Wen-Ping Qin, Dan-Dan Shen, Xue-Qi Liu, Xu-Dong Sun, Yi-Chao Zheng, Hong-Min Liu
Inhibition of lysine-specific demethylase 1 (LSD1) has recently emerged as an attractive therapeutic target for treating cancer and other diseases. As a continuity of our ongoing effort to identify novel small-molecule LSD1-inhibitors, we designed and synthesized a series of resveratrol derivatives, which were shown to be potent inhibitors of LSD1. Among them, compounds 4e and 4m displayed the most potent LSD1-inhibitory activities in enzyme assays, with IC50 values of 121 nM and 123 nM, respectively. Biochemistry study and docking analysis indicated that compounds 4e and 4m were reversible LSD1 inhibitors...
November 16, 2016: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/27882656/targeting-cancer-with-pcpa-drug-conjugates-lsd1-inhibition-triggered-release-of-4-hydroxytamoxifen
#20
Yosuke Ota, Yukihiro Itoh, Asako Kaise, Kiminori Ohta, Yasuyuki Endo, Mitsuharu Masuda, Yoshihiro Sowa, Toshiyuki Sakai, Takayoshi Suzuki
Targeting cancer with small molecule prodrugs should help overcome problems associated with conventional cancer-targeting methods. Herein, we focused on lysine-specific demethylase 1 (LSD1) to trigger the controlled release of anticancer drugs in cancer cells, where LSD1 is highly expressed. Conjugates of the LSD1 inhibitor trans-2-phenylcyclopropylamine (PCPA) were used as novel prodrugs to selectively release anticancer drugs by LSD1 inhibition. As PCPA-drug conjugate (PDC) prototypes, we designed PCPA-tamoxifen conjugates 1 a and 1 b, which released 4-hydroxytamoxifen in the presence of LSD1 in vitro...
December 23, 2016: Angewandte Chemie
keyword
keyword
18614
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"