keyword
https://read.qxmd.com/read/38338834/bioinformatics-and-experimental-validation-for-identifying-biomarkers-associated-with-amg510-sotorasib-resistance-in-kras-g12c-mutated-lung-adenocarcinoma
#1
JOURNAL ARTICLE
Peng Lin, Wei Cheng, Xin Qi, Pinglu Zhang, Jianshe Xiong, Jing Li
The Kirsten rat sarcoma viral oncogene homolog (KRAS)G12C mutation is prevalent in lung adenocarcinoma (LUAD), driving tumor progression and indicating a poor prognosis. While the FDA-approved AMG510 (Sotorasib) initially demonstrated efficacy in treating KRASG12C -mutated LUAD, resistance emerged within months. Data from AMG510 treatment-resistant LUAD (GSE204753) and single-cell datasets (GSE149655) were analyzed. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were used to explore enriched signaling pathways, nomogram models were constructed, and transcription factors predicting resistance biomarkers were predicted...
January 26, 2024: International Journal of Molecular Sciences
https://read.qxmd.com/read/37969738/the-f-box-only-protein-44-regulates-pregnane-x-receptor-protein-level-by-ubiquitination-and-degradation
#2
JOURNAL ARTICLE
Rebecca R Florke Gee, Andrew D Huber, Jing Wu, Richa Bajpai, Allister J Loughran, Shondra M Pruett-Miller, Taosheng Chen
Pregnane X receptor (PXR) is a ligand-activated nuclear receptor that transcriptionally upregulates drug-metabolizing enzymes [ e . g ., cytochrome P450 3A4 (CYP3A4)] and transporters. Although the regulation of PXR target genes is well-characterized, less is known about the regulation of PXR protein level. By screening an RNAi library, we identified the F-box-only protein 44 (FBXO44) as a novel E3 ligase for PXR. PXR abundance increases upon knockdown of FBXO44, and, inversely, decreases upon overexpression of FBXO44...
November 2023: Acta Pharmaceutica Sinica. B
https://read.qxmd.com/read/37595030/steerable-microneedles-enabling-deep-delivery-of-photosensitizers-and-crispr-cas9-systems-for-effective-combination-cancer-therapy
#3
JOURNAL ARTICLE
Tong Wang, Gang Chen, Shuangshuang Zhang, Dazhao Li, Guanjun Wei, Xiaomei Zhao, Yang Liu, Dawei Ding, Xuenong Zhang
Although gene therapy has shown prospects in treating triple-negative breast cancer, it is insufficient to treat such a malignant tumor. Herein, nanoparticles (NPs)-embedded dissolving microneedles (IR780-PL/pFBXO44@MNs) with steerable and flectional property were developed to achieve the codelivery of FBXO44-targeted CRISPR/Cas9 plasmids (pFBXO44) and hydrophobic photosensitizers. For improved NP penetration in tumor tissue, collagenase@MNs were preapplied to degrade the tumor matrix. Under light irradiation, IR780 exhibited remarkable phototherapy, while the escape efficiency of NPs from lysosomes was improved...
August 18, 2023: Nano Letters
https://read.qxmd.com/read/36774361/integrative-proteomic-characterization-of-adenocarcinoma-of-esophagogastric-junction
#4
JOURNAL ARTICLE
Shengli Li, Li Yuan, Zhi-Yuan Xu, Jing-Li Xu, Gui-Ping Chen, Xiaoqing Guan, Guang-Zhao Pan, Can Hu, Jinyun Dong, Yi-An Du, Li-Tao Yang, Mao-Wei Ni, Rui-Bin Jiang, Xiu Zhu, Hang Lv, Han-Dong Xu, Sheng-Jie Zhang, Jiang-Jiang Qin, Xiang-Dong Cheng
The incidence of adenocarcinoma of the esophagogastric junction (AEG) has been rapidly increasing in recent decades, but its molecular alterations and subtypes are still obscure. Here, we conduct proteomics and phosphoproteomics profiling of 103 AEG tumors with paired normal adjacent tissues (NATs), whole exome sequencing of 94 tumor-NAT pairs, and RNA sequencing in 83 tumor-NAT pairs. Our analysis reveals an extensively altered proteome and 252 potential druggable proteins in AEG tumors. We identify three proteomic subtypes with significant clinical and molecular differences...
February 11, 2023: Nature Communications
https://read.qxmd.com/read/35713327/focal-facial-dermal-dysplasias-type-iii-two-families-with-setleis-syndrome-in-china
#5
JOURNAL ARTICLE
Qiaoyu Cao, Shuai Zhang, Jianbo Wang, Yumeng Wang, Chaolan Pan, Xinyi Wang, Anqi Zhao, Xiao Chen, Pingping Qin, Shoumin Zhang, Zhirong Yao, Dong Lv, Yali Yang, Ming Li
Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14...
June 17, 2022: Journal of Dermatology
https://read.qxmd.com/read/34777457/evaluation-of-seasonal-heat-stress-on-transcriptomic-profiles-and-global-dna-methylation-of-bovine-oocytes
#6
JOURNAL ARTICLE
Fabian A Diaz, Emilio J Gutierrez-Castillo, Brittany A Foster, Paige T Hardin, Kenneth R Bondioli, Zongliang Jiang
Heat stress affects oocyte developmental competence and is a major cause of reduced fertility in heat stressed cattle. Negative effects of heat stress on the oocyte have been observed at morphological, biochemical and developmental levels. However, the mechanisms by which heat stress affects the oocyte at the transcriptional and epigenetic levels remain to be further elucidated. Here we aimed to investigate the effect of heat stress on oocyte quality, transcriptomic profiles and DNA methylation of oocytes collected through the transition from spring to summer under Louisiana conditions...
2021: Frontiers in Genetics
https://read.qxmd.com/read/34150004/identification-of-candidate-targets-for-the-diagnosis-and-treatment-of-atherosclerosis-by-bioinformatics-analysis
#7
JOURNAL ARTICLE
Yan Gu, Xiao Ma, Jing Li, Yuhong Ma, Yun Zhang
Atherosclerosis, a chronic inflammatory disease, is the primary cause of most cardiovascular diseases. Circular RNAs (circRNAs) were reported to serve as post-transcriptional regulators and diagnostic markers in various diseases, but the underlying correlation between circRNAs and atherosclerosis remains elusive. In this study, we downloaded the microarray dataset GSE107522 from the Gene Expression Omnibus (GEO) and identified nine differentially expressed circRNAs (DECs). DECs expression in exosomes were investigated, and hsa_circ_0005699 was selected for subsequent analysis...
2021: American Journal of Translational Research
https://read.qxmd.com/read/33745150/genome-wide-association-study-of-stage-iii-iv-grade-c-periodontitis-former-aggressive-periodontitis-in-a-spanish-population
#8
JOURNAL ARTICLE
Alicia de Coo, Raquel Cruz, Inés Quintela, David Herrera, Mariano Sanz, Pedro Diz, Segundo Rodríguez Grandío, Nuria Vallcorba, Isabel Ramos, Alfonso Oteo, Cristina Serrano, Alejandro Esmatges, Francisco Enrile, Leopoldo Mateos, Roberto García, Pablo Álvarez-Novoa, Blas Noguerol, Ion Zabalegui, José Blanco-Moreno, Ángel Alonso, Ramón Lorenzo, Angel Carracedo, Juan Blanco
AIM: To identify loci associated with stages III/IV, grade C periodontitis (PIII/IV-C) through a genome-wide association study (GWAS). MATERIALS AND METHODS: 441 Caucasian Spanish PIII/IV-C cases from the SEPA Network of Research Clinics and 1141 controls from the Banco Nacional de ADN were genotyped with "Axiom Spain Biobank Array," which contains 757836 markers, including rare and low-frequency Spanish variants. The analysis of the individual association and subsequently the gene-level analysis with Sequence Kernel Association Test (SKAT) were carried out adjusting for age, sex and PC1 covariates...
July 2021: Journal of Clinical Periodontology
https://read.qxmd.com/read/33681705/targeting-fbxo44-suv39h1-elicits-tumor-cell-specific-dna-replication-stress-and-viral-mimicry
#9
COMMENT
Jia Z Shen, Charles Spruck
Repetitive elements (REs) are normally transcriptionally silenced in somatic cells by repressive epigenetic modifications, which are thought to include DNA methylation and histone modifications such as deacetylation, H3K9me3, and H4K20me3. Although, it is unclear how RE silencing is maintained through DNA replication cycles in rapidly growing cancer cells. On the other hand, the reactivation of endogenous retroelements beyond a threshold level of tolerance in cancer cells, such as by treatment with DNA demethylating agents or HDAC or LSD1 inhibitors, can induce viral mimicry responses that augment certain cancer therapies, including immunotherapy...
February 18, 2021: Cell Stress
https://read.qxmd.com/read/33451987/fbxo44-silences-repetitive-elements-during-dna-replication-in-cancer
#10
JOURNAL ARTICLE
(no author information available yet)
FBXO44 bound H3K9me3 at replication forks, recruiting a complex to repress repetitive elements.
January 15, 2021: Cancer Discovery
https://read.qxmd.com/read/33357448/fbxo44-promotes-dna-replication-coupled-repetitive-element-silencing-in-cancer-cells
#11
JOURNAL ARTICLE
Jia Z Shen, Zhixin Qiu, Qiulian Wu, Darren Finlay, Guillermina Garcia, Dahui Sun, Juha Rantala, William Barshop, Jennifer L Hope, Ryan C Gimple, Olle Sangfelt, Linda M Bradley, James Wohlschlegel, Jeremy N Rich, Charles Spruck
Repetitive elements (REs) compose ∼50% of the human genome and are normally transcriptionally silenced, although the mechanism has remained elusive. Through an RNAi screen, we identified FBXO44 as an essential repressor of REs in cancer cells. FBXO44 bound H3K9me3-modified nucleosomes at the replication fork and recruited SUV39H1, CRL4, and Mi-2/NuRD to transcriptionally silence REs post-DNA replication. FBXO44/SUV39H1 inhibition reactivated REs, leading to DNA replication stress and stimulation of MAVS/STING antiviral pathways and interferon (IFN) signaling in cancer cells to promote decreased tumorigenicity, increased immunogenicity, and enhanced immunotherapy response...
January 21, 2021: Cell
https://read.qxmd.com/read/33008920/n-terminal-targeting-of-regulator-of-g-protein-signaling-protein-2-for-f-box-only-protein-44-mediated-proteasomal-degradation
#12
JOURNAL ARTICLE
Harrison J McNabb, Stephanie Gonzalez, Christine S Muli, Benita Sjögren
Regulator of G protein signaling (RGS) proteins are negative modulators of G protein signaling that have emerged as promising drug targets to improve specificity and reduce side effects of G protein-coupled receptor-related therapies. Several small molecule RGS protein inhibitors have been identified; however, enhancing RGS protein function is often more clinically desirable but presents a challenge. Low protein levels of RGS2 are associated with various pathologies, including hypertension and heart failure...
December 2020: Molecular Pharmacology
https://read.qxmd.com/read/26460611/the-structural-differences-between-a-glycoprotein-specific-f-box-protein-fbs1-and-its-homologous-protein-fbg3
#13
JOURNAL ARTICLE
Taichi Kumanomidou, Kazuya Nishio, Kenji Takagi, Tomomi Nakagawa, Atsuo Suzuki, Takashi Yamane, Fuminori Tokunaga, Kazuhiro Iwai, Arisa Murakami, Yukiko Yoshida, Keiji Tanaka, Tsunehiro Mizushima
The Skp1-Cul1-F-box protein (SCF) complex catalyzes protein ubiquitination in diverse cellular processes and is one of the best-characterized ubiquitin ligases. F-box proteins determine the substrate specificities of SCF ubiquitin ligases. Among these, Fbs1/FBG1/FBXO2, Fbs2/FBG2/FBXO6, and Fbs3/FBG5/FBXO27 recognize the N-glycans of glycoproteins, whereas FBG3/FBXO44 has no sugar-binding activity, despite the high sequence homology and conservation of the residues necessary for oligosaccharide binding between Fbs1-3 and FBG3...
2015: PloS One
https://read.qxmd.com/read/25970626/fbxo44-mediated-degradation-of-rgs2-protein-uniquely-depends-on-a-cullin-4b-ddb1-complex
#14
JOURNAL ARTICLE
Benita Sjögren, Steven Swaney, Richard R Neubig
The ubiquitin-proteasome system for protein degradation plays a major role in regulating cell function and many signaling proteins are tightly controlled by this mechanism. Among these, Regulator of G Protein Signaling 2 (RGS2) is a target for rapid proteasomal degradation, however, the specific enzymes involved are not known. Using a genomic siRNA screening approach, we identified a novel E3 ligase complex containing cullin 4B (CUL4B), DNA damage binding protein 1 (DDB1) and F-box protein 44 (FBXO44) that mediates RGS2 protein degradation...
2015: PloS One
https://read.qxmd.com/read/23185754/-study-on-gene-differential-expressions-of-substance-and-energy-metabolism-in-chronic-superficial-gastritis-patients-of-pi-deficiency-syndrome-and-of-pi-wei-hygropyrexia-syndrome
#15
JOURNAL ARTICLE
Ze-Min Yang, Wei-Wen Chen, Ying-Fang Wang
OBJECTIVE: To analyze the metabolic levels of energy and substance in chronic superficial gastritis (CSG) patients of Pi deficiency syndrome (PDS) and of Pi-Wei hygropyrexia syndrome (PWHS), including lipid, protein, nucleic acid, carbohydrate, trace element, and energy metabolism, and to study the pathogenesis mechanism of PDS from substance and energy metabolisms. METHODS: Recruited were 8 CSG patients who visited at First Affiliated Hospital of Guangzhou University of Traditional Chinese Medicine and Guangdong Provincial Hospital of Traditional Chinese Medicine from June 2004 to March 2005, including 4 patients of PDS and 4 of PWHS...
September 2012: Chinese Journal of Integrated Traditional and Western Medicine
https://read.qxmd.com/read/23086937/the-f-box-protein-fbxo44-mediates-brca1-ubiquitination-and-degradation
#16
JOURNAL ARTICLE
Yunzhe Lu, Jiezhi Li, Dongmei Cheng, Balaji Parameswaran, Shaohua Zhang, Zefei Jiang, P Renee Yew, Junmin Peng, Qinong Ye, Yanfen Hu
BRCA1 mutations account for a significant proportion of familial breast and ovarian cancers. In addition, reduced BRCA1 protein is associated with sporadic cancer cases in these tissues. At the cellular level, BRCA1 plays a critical role in multiple cellular functions such as DNA repair and cell cycle checkpoint control. Its protein level is regulated in a cell cycle-dependent manner. However, regulation of BRCA1 protein stability is not fully understood. Our earlier study showed that the amino terminus of BRCA1 harbors a degron sequence that is sufficient and necessary for conferring BRCA1 degradation...
November 30, 2012: Journal of Biological Chemistry
https://read.qxmd.com/read/18203720/diversity-in-tissue-expression-substrate-binding-and-scf-complex-formation-for-a-lectin-family-of-ubiquitin-ligases
#17
JOURNAL ARTICLE
Kevin A Glenn, Rick F Nelson, Hsiang M Wen, Adam J Mallinger, Henry L Paulson
Post-translational modification of proteins regulates many cellular processes. Some modifications, including N-linked glycosylation, serve multiple functions. For example, the attachment of N-linked glycans to nascent proteins in the endoplasmic reticulum facilitates proper folding, whereas retention of high mannose glycans on misfolded glycoproteins serves as a signal for retrotranslocation and ubiquitin-mediated proteasomal degradation. Here we examine the substrate specificity of the only family of ubiquitin ligase subunits thought to target glycoproteins through their attached glycans...
May 9, 2008: Journal of Biological Chemistry
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