A5000762926- Lung Cancer Research Studies
- Peptidase Inhibition and Analysis
- Neuroendocrine Tumor Research Advances
- Signaling Pathways in Disease
- Fibroblast Growth Factor Research
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- Cancer-related gene regulation
- Genomics and Chromatin Dynamics
- Cancer Mechanisms and Therapy
- Histone Deacetylase Inhibitors Research
- Glycosylation and Glycoproteins Research
- Cancer Cells and Metastasis
- FOXO transcription factor regulation
- Bone Metabolism and Diseases
- Cancer therapeutics and mechanisms
- Genetics, Bioinformatics, and Biomedical Research
- Heat shock proteins research
- DNA Repair Mechanisms
- Gestational Trophoblastic Disease Studies
- Chromatin Remodeling and Cancer
- Metastasis and carcinoma case studies
- ATP Synthase and ATPases Research
- Neuroblastoma Research and Treatments
- RNA Research and Splicing
Kyungpook National University
2022-2025
University of Virginia
2016-2024
University of Virginia Health System
2022
Chung-Ang University
2009-2020
University of Virginia Cancer Center
2018
, encoding an acetyltransferase, is among the most frequently mutated genes in small cell lung cancer (SCLC), a deadly neuroendocrine tumor type. We report acceleration of SCLC upon
Posttranslational modifications of the Forkhead family transcription factor, FOXO1, have been known to important regulatory implications in its diverse activities. Several types including acetylation, phosphorylation, and ubiquitination, reported. However, lysine methylation FOXO1 has not yet identified. Here, we reported that is methylated by G9a at K273 residue vitro vivo. Methylation increased interaction between a specific E3 ligase, SKP2, decreased protein stability. In addition,...
Small cell lung cancer (SCLC) is a devastating neuroendocrine carcinoma. MYCL (L-Myc) frequently amplified in human SCLC, but its roles SCLC progression are poorly understood. We isolated preneoplastic cells from mouse model of and found that ectopic expression L-Myc, c-Myc, or N-Myc conferred tumor-forming capacity. focused on which promoted pre-rRNA synthesis transcriptional programs associated with ribosomal biogenesis. Deletion Mycl two genetically engineered models resulted strong...
The methylation of histone H3 lysine 79 (H3K79) is an active chromatin marker and prominent in actively transcribed regions the genome; however, demethylase H3K79 remains unknown despite intensive research. Here, we show that KDM2B, also known as FBXL10 a member Jumonji C family proteins for its H3K36 activity, di- trimethyl demethylase. We demonstrate KDM2B induces transcriptional repression HOXA7 MEIS1 via occupancy promoters demethylation H3K79. Furthermore, genome-wide analysis suggests...
Histone lysine methylation and demethylation are considered critical steps in transcriptional regulation. In this report, we performed chromatin immunoprecipitation with microarray technology (ChIP-chip) analysis to examine the genome-wide occupancy of H3K9-me2 during all-trans-retinoic acid (ATRA)-induced differentiation HL-60 promyelocytic leukemia cells. Using approach, found that KDM3B, which contains a JmjC domain, was downregulated through recruitment corepressor complex. Furthermore,...
Histone lysine methylation, as one of the most important factors in transcriptional regulation, is associated with a various physiological conditions. Using bioinformatics search, we identified and subsequently cloned mouse SET domain containing 3 (SETD3) (Su(var)3-9, Enhancer-of-zeste Trithorax) Rubis-subs-bind domains. SETD3 novel histone H3K4 H3K36 methyltransferase activation activity. expressed abundantly muscular tissues and, when overexpressed, activates transcription muscle-related...
EP300, a transcription coactivator important in proliferation and differentiation, is frequently mutated diverse cancer types, including small cell lung (SCLC). While these mutations are thought to result loss of EP300 function, the impact on tumorigenesis remains largely unknown. Here, we demonstrate that mutants lacking acetyltransferase domain accelerate tumor development mouse models SCLC. However, unexpectedly, complete
Oncogenic KRas activates mitochondrial fission through Erk-mediated phosphorylation of the GTPase Drp1. Drp1 deletion inhibits tumorigenesis KRas-driven pancreatic cancer, but role dynamics in other Ras-driven malignancies is poorly defined. Here we show that vitro and vivo growth lung adenocarcinoma unaffected by inhibited Opa1, regulates inner membrane fusion proper cristae morphology. Mechanistically, Opa1 knockout disrupts morphology electron transport chain (ETC) assembly activity,...
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1) is a key epigenetic regulator of DNA methylation maintenance heterochromatin formation. The roles UHRF1 in damage repair also have been emphasized recent years. However, the regulatory mechanism remains elusive. In this study, we showed that methylated by SET7 demethylation catalyzed LSD1. addition, induced response to its phosphorylation S phase prerequisite for interaction SET7. Furthermore, catalyzes conjugation polyubiquitin...
Histone H3K9 methyltransferase (HMTase) G9a-mediated transcriptional repression is a major epigenetic silencing mechanism. UHRF1 (ubiquitin-like with PHD and ring finger domains 1) binds to hemimethylated DNA plays an essential role in the maintenance of methylation. Here, we provide evidence that transcriptionally downregulated by HMTase G9a. We found increased expression G9a along transcription factor YY1 specifically represses during TPA-mediated leukemia cell differentiation. Using ChIP...
Small cell lung cancer (SCLC) remains a recalcitrant disease where limited therapeutic options have not improved overall survival, and approved targeted therapies are lacking. Amplification of the tyrosine kinase receptor FGFR1 (fibroblast growth factor 1) is one few actionable alterations found in SCLC genome. However, efforts to develop for FGFR1-amplified hindered by critical gaps knowledge around molecular origins mediators FGFR1-driven signaling as well physiologic impact targeting...
Tumor cell plasticity contributes to intratumoral heterogeneity and therapy resistance. Through plasticity, some lung adenocarcinoma (LUAD) cells transform into neuroendocrine (NE) tumor cells. However, the mechanisms of NE remain unclear. CRACD (capping protein inhibiting regulator actin dynamics), a capping inhibitor, is frequently inactivated in cancers. knockout (KO) sufficient de-repress NE-related gene expression pulmonary epithelium LUAD In mouse models, Cracd KO increases with...
Post-translational modifications of histones have been demonstrated to play important roles in the regulation chromatin structure and transcriptional regulation. In histone modification, methylated lysine has an role The evolutionarily conserved SET domain was first identified Drosophila proteins: Suppressor variegation (Su(var)3-9), Enhancer zeste (E(z)), Trithorax. domain-containing proteins methyltransferase (HMTase) activity via domain. Using a bioinformatics approach, we cloned...
Abstract Histone lysine methylation contributes to transcriptional regulation by serving as a platform for the recruitment of various cofactors. Intense studies have been conducted elucidating functional meaning H3K79 and date, only known HMTase responsible modification was DOT1L. In this study, we report that MMSET isoform RE-IIBP has activity H3K79. It uncovered up-regulates MEIS1 transcription through via promoter. By means proteomic biochemical analysis, association with E3 ubiquitin...
The balance between major DNA double-strand break (DSB) repair pathways is influenced by binding of the Ku complex, a XRCC5/6 heterodimer, to DSB ends, initiating non-homologous end joining (NHEJ) but preventing additional resection and homologous recombination (HR). However, key molecular cue for recruitment sites unknown. Here, we report that FOXL2, forkhead family transcriptional factor, directs pathway choice acetylation-dependent Ku. Upon induction, SIRT1 translocates nucleus...
Functional characterisation of cell-type-specific regulatory networks is key to establish a causal link between genetic variation and phenotype. The osteoclast offers unique model for interrogating the contribution co-regulated genes in vivo phenotype as its multinucleation resorption activities determine quantifiable skeletal traits. Here we took advantage trans-regulated gene network (MMnet, macrophage network) which found be significantly enriched GWAS variants associated with...
We report that H3K9 HMTase G9a activates transcription of the cell cycle regulatory gene, p21 , in p53 ‐null H1299 cells. Positive regulation by is independent its activity. demonstrate upregulates via interaction with PCAF, and provide evidence activating complex recruited to promoter upon DNA damage‐inducing agent etoposide treatment. Our study suggests decreases proliferation viability increasing level p21‐mediated apoptosis. results suggest functions as a coactivator for transcription,...