1,338 results match your criteria aberrant mitogen-activated

Quantitative description of the interactions among kinase cascades underlying long-term plasticity of Aplysia sensory neurons.

Sci Rep 2021 Jul 22;11(1):14931. Epub 2021 Jul 22.

Department of Neurobiology and Anatomy, W.M. Keck Center for the Neurobiology of Learning and Memory, McGovern Medical School, The University of Texas Health Center At Houston, 6431 Fannin Street, Suite MSB 7.046, Houston, TX, 77030, USA.

Kinases play critical roles in synaptic and neuronal changes involved in the formation of memory. However, significant gaps exist in the understanding of how interactions among kinase pathways contribute to the mechanistically distinct temporal domains of memory ranging from short-term memory to long-term memory (LTM). Activation of protein kinase A (PKA) and mitogen-activated protein kinase (MAPK)-ribosomal S6 kinase (RSK) pathways are critical for long-term enhancement of neuronal excitability (LTEE) and long-term synaptic facilitation (LTF), essential processes in memory formation. Read More

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Combination Treatment With Inhibitors of ERK and Autophagy Enhances Antitumor Activity of Betulinic Acid in Non-small-Cell Lung Cancer and .

Front Pharmacol 2021 29;12:684243. Epub 2021 Jun 29.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Aberrant activation of the Ras-ERK signaling pathway drives many important cancer phenotypes, and several inhibitors targeting such pathways are under investigation and/or approved by the FDA as single- or multi-agent therapy for patients with melanoma and non-small-cell lung cancer (NSCLC). Here, we show that betulinic acid (BA), a natural pentacyclic triterpenoid, inhibits cell proliferation, and induces apoptosis and protective autophagy in NSCLC cells. Thus, the cancer cell killing activity of BA is enhanced by autophagy inhibition. Read More

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Insights Into Transcriptome Profiles Associated With Wooden Breast Myopathy in Broilers Slaughtered at the Age of 6 or 7 Weeks.

Front Physiol 2021 28;12:691194. Epub 2021 Jun 28.

National Center for Genetic Engineering and Biotechnology (BIOTEC), Thailand Science Park, Pathum Thani, Thailand.

Transcriptomes associated with wooden breast (WB) were characterized in broilers at two different market ages. Breasts () were collected, 20-min postmortem, from male Ross 308 broilers slaughtered at 6 and 7 weeks of age. The breasts were classified as "non-WB" or "WB" based on palpation hardness scoring (non-WB = no abnormal hardness, WB = consistently hardened). Read More

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Neutrophil extracellular traps contribute to immune dysregulation in bullous pemphigoid via inducing B-cell differentiation and antibody production.

FASEB J 2021 07;35(7):e21746

Department of Dermatology, Xijing Hospital, Fourth Military Medical University, Xi'an, China.

Bullous pemphigoid (BP), an autoimmune skin disease, is characterized by autoantibodies against hemidesmosomal proteins in the skin and mucous membranes. Neutrophils infiltrate BP skin lesions, however, their role in immune dysregulation remains unclear. We investigated whether BP involves aberrant neutrophil extracellular traps (NETs) formation in skin lesions and circulation; and examined the triggers and deleterious immuno-inflammatory consequences. Read More

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Transcriptomic Landscape of Circulating Mononuclear Phagocytes in Langerhans Cell Histiocytosis at Single-cell Level.

Blood 2021 Jun 16. Epub 2021 Jun 16.

Affiliated Hospital of Academy of Military Medical Sciences, Beijing, China.

Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm caused by aberrant activation of the mitogen-activated protein kinase (MAPK) pathway. Circulating myeloid cells from patients often carry disease-associated mutations and can be differentiated into langerinhigh LCH-like cells in vitro, but their detailed immune-phenotypic and molecular profiles are lacking and could shed key insights into disease biology. Here we recruited 217 pediatric LCH patients and took blood and tissue samples for BRAFV600E analysis. Read More

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Extensive remodeling of the extracellular matrix during aging contributes to age-dependent impairments of muscle stem cell functionality.

Cell Rep 2021 Jun;35(10):109223

Leibniz Institute on Aging, Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany. Electronic address:

During aging, the regenerative capacity of skeletal muscle decreases due to intrinsic changes in muscle stem cells (MuSCs) and alterations in their niche. Here, we use quantitative mass spectrometry to characterize intrinsic changes in the MuSC proteome and remodeling of the MuSC niche during aging. We generate a network connecting age-affected ligands located in the niche and cell surface receptors on MuSCs. Read More

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Enhanced G1 arrest and apoptosis via MDM4/MDM2 double knockdown and MEK inhibition in wild-type colon and gastric cancer cells with aberrant KRAS signaling.

Oncol Lett 2021 Jul 25;22(1):558. Epub 2021 May 25.

Department of Gastroenterology, Institute of Clinical Medicine, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305-8575, Japan.

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin-ligase activity. MDM4 cooperates with MDM2-mediated p53 degradation, directly inhibiting p53 transcription by binding to its transactivation domain. Our previous study reported that the simultaneous inhibition of MDM2 and MDM4 using nutlin-3 (an inhibitor of the MDM2-p53 interaction) and chimeric small interfering RNA with DNA-substituted seed arms (named chiMDM2 and chiMDM4) more potently activated p53 than the MDM2 or MDM4 inhibitor alone and synergistically augmented antitumor effects in various types of cancer cells with the wild-type (wt) . Read More

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Amelioration of lipopolysaccharide-induced memory impairment in equilibrative nucleoside transporter-2 knockout mice is accompanied by the changes in glutamatergic pathways.

Brain Behav Immun 2021 Aug 28;96:187-199. Epub 2021 May 28.

School of Pharmacy, College of Medicine, National Taiwan University, Taipei, Taiwan. Electronic address:

Neuroinflammation has been implicated in cognitive deficits in neurological and neurodegenerative diseases. Lipopolysaccharide (LPS)-induced neuroinflammation and the breakdown of the blood-brain barrier can be attenuated in mice with equilibrative nucleoside transporter-2 (ENT2/Ent2) deletion. The present study was aimed to investigate the role of ENT2 in cognitive and neuronal functions under physiological and inflammatory conditions, in terms of behavioral performance and synaptic plasticity in saline- and LPS-treated Ent2 knockout (KO) mice and their wild-type (WT) littermate controls. Read More

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TAK1 signaling is a potential therapeutic target for pathological angiogenesis.

Angiogenesis 2021 Aug 10;24(3):453-470. Epub 2021 May 10.

Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, TAS, 7000, Australia.

Angiogenesis plays a critical role in both physiological responses and disease pathogenesis. Excessive angiogenesis can promote neoplastic diseases and retinopathies, while inadequate angiogenesis can lead to aberrant perfusion and impaired wound healing. Transforming growth factor β activated kinase 1 (TAK1), a member of the mitogen-activated protein kinase kinase kinase family, is a key modulator involved in a range of cellular functions including the immune responses, cell survival and death. Read More

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Wallenda-Nmo Axis Regulates Growth via Hippo Signaling.

Front Cell Dev Biol 2021 16;9:658288. Epub 2021 Apr 16.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

Both Hippo signaling pathways and cell polarity regulation are critical for cell proliferation and the maintenance of tissue homeostasis, despite the well-established connections between cell polarity disruption and Hippo inactivation, the molecular mechanism by which aberrant cell polarity induces Hippo-mediated overgrowth remains underexplored. Here we use wing discs as a model and identify the Wnd-Nmo axis as an important molecular link that bridges loss-of-cell polarity-triggered Hippo inactivation and overgrowth. We show that Wallenda (Wnd), a MAPKKK (mitogen-activated protein kinase kinase kinase) family member, is a novel regulator of Hippo pathways in and that overexpression of Wnd promotes growth via Nemo (Nmo)- mediated Hippo pathway inactivation. Read More

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Stochastic modulation evidences a transitory EGF-Ras-ERK MAPK activity induced by PRMT5.

Comput Biol Med 2021 06 20;133:104339. Epub 2021 Apr 20.

Institute for Research in Biomedicine (IRB Barcelona), Barcelona Institute of Science and Technology (BIST), Barcelona, Spain; CIBER of Diabetes and Associated Metabolic Diseases, Barcelona, Spain; Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, Barcelona, Spain.

The extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway involves a three-step cascade of kinases that transduce signals and promote processes such as cell growth, development, and apoptosis. An aberrant response of this pathway is related to the proliferation of cell diseases and tumors. By using simulation modeling, we document that the protein arginine methyltransferase 5 (PRMT5) modulates the MAPK pathway and thus avoids an aberrant behavior. Read More

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Allosteric Kinase Inhibitors Reshape MEK1 Kinase Activity Conformations in Cells and In Silico.

Biomolecules 2021 03 30;11(4). Epub 2021 Mar 30.

Institute of Biochemistry and Center for Molecular Biosciences Innsbruck, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria.

Mutations at different stages of the mitogen-activated protein kinase (MAPK) signaling pathway lead to aberrant activation of the involved protein kinase entities. These oncogenic modifications alter signal propagation which converge on the gatekeeper kinases MEK1/2, transmitting the input signal to ERK1/2. Thus, targeted MEK inhibition causes qualitative alterations of carcinogenic MAPK signals. Read More

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TORC2/3-mediated DUSP1 upregulation is essential for human decidualization.

Reproduction 2021 05;161(5):573-580

Laboratory for Reproductive Immunology, NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Shanghai Key Laboratory of Female Reproductive Endocrine Related Diseases, Hospital of Obstetrics and Gynecology, Fudan University Shanghai Medical College, Shanghai, People's Republic of China.

Decidualization is the functional transformation process of endometrium in response to ovarian steroids dedicated to support embryo development. Defective decidualization is closely associated with various pregnancy complications such as recurrent miscarriage (RM). Dual specificity MAPK phosphatases (MKPs) are a family of phosphatases specifically regulating mitogen-activated protein kinase (MAPK) signaling with dual specificity for threonine and tyrosine. Read More

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Fibroblast growth factor receptor () gene: pathogenesis and treatment implications in urothelial carcinoma of the bladder.

J Clin Pathol 2021 Aug 17;74(8):491-495. Epub 2021 Mar 17.

Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA

Dysregulation of fibroblast growth factor receptors () has been implicated in several human malignancies, including urothelial carcinoma. In urothelial carcinoma, the oncogenic role of mutated is mediated by the RAS-mitogen-activated protein kinase pathway, resembling the effects observed with activated Activating somatic mutations of are clustered in three hotspots in exons 7, 10 and 15, and are almost always missense mutations leading to amino acid substitution in the external, transmembrane or intracellular regions of the receptor. A fusion of to transforming acid coiled-coil containing protein 3, amplification and alternative splicing leading to aberrant activation are less common molecular alterations. Read More

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Whole-genome methylation analysis reveals novel epigenetic perturbations of congenital scoliosis.

Mol Ther Nucleic Acids 2021 Mar 10;23:1281-1287. Epub 2021 Feb 10.

Department of Orthopedic Surgery, State Key Laboratory of Complex Severe and Rare Diseases, Beijing Key Laboratory for Genetic Research of Skeletal Deformity, Key Laboratory of Big Data for Spinal Deformities, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100730, China.

Congenital scoliosis (CS) is a congenital disease caused by malformations of vertebrae. Recent studies demonstrated that DNA modification could contribute to the pathogenesis of disease. This study aims to identify epigenetic perturbations that may contribute to the pathogenesis of CS. Read More

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p38 MAPK Inhibition Mitigates Hypoxia-Induced AR Signaling in Castration-Resistant Prostate Cancer.

Cancers (Basel) 2021 Feb 17;13(4). Epub 2021 Feb 17.

Princess Margaret Cancer Centre, University Health Network, Toronto, ON M5G 2C1, Canada.

Background: Aberrant androgen receptor (AR) signaling is a major driver of castration-resistant prostate cancer (CRPC). Tumor hypoxia increases AR signaling and is associated with treatment resistance in prostate cancer. Heat shock protein 27 (Hsp27) is a molecular chaperone that is activated in response to heat shock and hypoxia. Read More

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February 2021

Differential regulation of β-catenin-mediated transcription via N- and C-terminal co-factors governs identity of murine intestinal epithelial stem cells.

Nat Commun 2021 03 1;12(1):1368. Epub 2021 Mar 1.

Department of Molecular Life Sciences, University of Zurich, Zurich, Switzerland.

The homeostasis of the gut epithelium relies upon continuous renewal and proliferation of crypt-resident intestinal epithelial stem cells (IESCs). Wnt/β-catenin signaling is required for IESC maintenance, however, it remains unclear how this pathway selectively governs the identity and proliferative decisions of IESCs. Here, we took advantage of knock-in mice harboring transgenic β-catenin alleles with mutations that specifically impair the recruitment of N- or C-terminal transcriptional co-factors. Read More

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FBXW11 deletion alleviates Alzheimer's disease by reducing neuroinflammation and amyloid-β plaque formation via repression of ASK1 signaling.

Biochem Biophys Res Commun 2021 Apr 25;548:104-111. Epub 2021 Feb 25.

Department of Neurology, Lanzhou University Second Hospital, Lanzhou, 730000, China. Electronic address:

Alzheimer's disease (AD) is a neurodegenerative disease with a complicated pathogenesis. F-box and WD-40 domain protein 11 (FBXW11), as a component of the SCF (Skp1-Cul1-F-box) E3 ubiquitin ligase complex, regulates multiple different signaling pathways. However, the effects of FBXW11 on AD progression and the underlying mechanisms have not been studied. Read More

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PBK expression predicts favorable survival in colorectal cancer patients.

Virchows Arch 2021 Feb 27. Epub 2021 Feb 27.

Department of Experimental Pathology and Tumor Biology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.

Colorectal cancer (CRC) is one of the most common gastrointestinal cancers worldwide with high morbidity and mortality rates. The discovery of small molecule anticancer reagents has significantly affected cancer therapy. However, the anticancer effects of these therapies are not sufficient to completely cure CRC. Read More

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February 2021

LOXL1 exerts oncogenesis and stimulates angiogenesis through the LOXL1-FBLN5/αvβ3 integrin/FAK-MAPK axis in ICC.

Mol Ther Nucleic Acids 2021 Mar 9;23:797-810. Epub 2021 Jan 9.

Department of Biliary-Pancreatic Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 200120, China.

Aberrant expression of lysyl oxidase-like 1 (LOXL1) reportedly leads to fibrous diseases. Recent studies have revealed its role in cancers. In this study, we observed an elevated level of LOXL1 in the tissues and sera of patients with intrahepatic cholangiocarcinoma (ICC) compared with levels in nontumor tissues and sera of unaffected individuals. Read More

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miR-322/miR-503 clusters regulate defective myoblast differentiation in myotonic dystrophy RNA-toxic by targeting Celf1.

Toxicol Res (Camb) 2021 Jan 5;10(1):29-39. Epub 2021 Jan 5.

Department of Cardiovascular, The First Affiliated Hospital of Nanchang University, No. 17, Yongwai Zheng Street, Nanchang, Jiangxi Province 330006, P. R. China.

Myotonic dystrophy (DM) is a genetic disorder featured by muscular dystrophy. It is caused by CUG expansion in the myotonic dystrophy protein kinase gene that leads to aberrant signaling and impaired myocyte differentiation. Many studies have shown that microRNAs are involved in the differentiation process of myoblasts. Read More

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January 2021

Epidermal growth factor upregulates the expression of A20 in hepatic cells via the MEK1/MSK1/p-p65 (Ser276) signaling pathway.

Am J Transl Res 2021 15;13(2):708-718. Epub 2021 Feb 15.

Department of Internal Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University Zhengzhou 450008, Henan, P. R. China.

Tumor necrosis factor α-induced protein 3 (A20) suppresses inflammation by inhibiting the activation of nuclear factor kappa B (NF-κB). The aberrant expression of A20 is reportedly correlated with tumor development in human malignancies, including hepatocellular carcinoma (HCC). Proinflammatory mediators, including tumor necrosis factor α (TNF-α), interleukin-1, and lipopolysaccharide, may induce A20 expression. Read More

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February 2021

RNA-binding protein QKI suppresses breast cancer via RASA1/MAPK signaling pathway.

Ann Transl Med 2021 Jan;9(2):104

Department of General Surgery, Huashan Hospital, Fudan University, Shanghai, China.

Background: RNA-binding protein Quaking (QKI) has been linked with the pathogenesis and development of various human malignancies. Herein, we explored the particular role of QKI in breast cancer (BC) progression.

Methods: The methods employed in the study included public dataset analysis, western blot, quantitative real-time PCR (qRT-PCR), cell count kit-8 (CCK8) assay, colony formation assay, flow cytometric analysis, RNA immunoprecipitation (RIP), messenger RNA (mRNA) stability assay, QKI overexpression and knockdown, and Ras p21 protein activator 1 (RASA1) knockdown. Read More

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January 2021

BRAF/MEK inhibitors for BRAF V600E-mutant cancers in non-approved setting: a case series.

Cancer Chemother Pharmacol 2021 03 3;87(3):437-441. Epub 2021 Feb 3.

Drug Development Unit, Sarah Cannon Research Institute, 93 Harley Street, London, W1G 6AD, UK.

The management of cancer has been traditionally dependent on the primary tumour type and specific histologic subtypes. Recently, the introduction of molecular profiling tools and its increasing use in clinical practice has facilitated the emergence of novel genomically driven treatment options within the standard of care landscape as well as in the clinical trial setting. One such aberration is mutation in v-Raf murine sarcoma viral oncogene homolog B (BRAF), which results in hyperactivation of RAS-RAF-MEK-ERK signaling in the Mitogen-activated protein kinases (MAPK) pathway. Read More

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miR-335-5p suppresses gastric cancer progression by targeting MAPK10.

Cancer Cell Int 2021 Jan 22;21(1):71. Epub 2021 Jan 22.

Department of Cell Biology and Genetics, Medical College of Yan'an University, Yan'an, 716000, Shaanxi, China.

Background: Recent studies have established the roles of microRNAs (miRNAs) in cancer progression. The aberrant expression of miR-335-5p has been reported in many cancers, including gastric cancer (GC). In this study, the precise roles of miR-335-5p in GC as well as the molecular mechanisms underlying its effects, including the role of its target MAPK10, were evaluated. Read More

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January 2021

ASK1/p38‑mediated NLRP3 inflammasome signaling pathway contributes to aberrant retinal angiogenesis in diabetic retinopathy.

Int J Mol Med 2021 02 24;47(2):732-740. Epub 2020 Dec 24.

Department of Ophthalmology, The Affiliated Wuxi No. 2 People's Hospital of Nanjing Medical University, Wuxi, Jiangsu 214002, P.R. China.

Diabetic retinopathy (DR) is the leading cause of blindness among the working‑age population in several countries. Despite the available treatments, some patients are diagnosed at the late stages of the disease when treatment is more difficult. Hence, it is crucial that novel targets are identified in order to improve the clinical therapy of DR. Read More

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February 2021

Whole-genome resequencing reveals aberrant autosomal SNPs affect chicken feathering rate.

Anim Biotechnol 2020 Dec 21:1-13. Epub 2020 Dec 21.

Sichuan Animal Science Academy, Chengdu, Sichuan, China.

Previous studies have shown that the feather growth rate of chicks is determined by two alleles located on the sex chromosome Z; however, in chicken production, feathering is usually not consistently controlled by the sex chromosome. To identify whether the feathering rate is related to autosomal inheritance, whole-genome resequencing was performed in eight chickens with slow- and fast-feathering rate. A total of 54,984 autosomal single nucleotide polymorphisms (SNPs) were identified, including 393 and 376 exonic SNPs in slow-feathering and fast-feathering chickens, respectively. Read More

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December 2020

Aberrant mitochondrial morphology and function associated with impaired mitophagy and DNM1L-MAPK/ERK signaling are found in aged mutant Parkinsonian LRRK2 mice.

Autophagy 2020 Dec 10:1-25. Epub 2020 Dec 10.

Division of Neurology, Department of Medicine, University of Hong Kong, Hong Kong, China.

Mitochondrial dysfunction causes energy deficiency and nigrostriatal neurodegeneration which is integral to the pathogenesis of Parkinson disease (PD). Clearance of defective mitochondria involves fission and ubiquitin-dependent degradation via mitophagy to maintain energy homeostasis. We hypothesize that LRRK2 (leucine-rich repeat kinase 2) mutation disrupts mitochondrial turnover causing accumulation of defective mitochondria in aging brain. Read More

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December 2020

MicroRNA-3613-5p Promotes Lung Adenocarcinoma Cell Proliferation through a RELA and AKT/MAPK Positive Feedback Loop.

Mol Ther Nucleic Acids 2020 Dec 26;22:572-583. Epub 2020 Sep 26.

School of Pharmacy, Guangdong Medical University, Dongguan, Guangdong 523808, P.R. China.

Aberrant activation of nuclear factor κB (NF-κB)/RELA is often found in lung adenocarcinoma (LUAD). In this study, we determined that microRNA-3613-5p (miR-3613-5p) plays a crucial role in RELA-mediated post-transcriptional regulation of LUAD cell proliferation. Expression of miR-3613-5p in clinical LUAD specimens is associated with poor prognosis in LUAD. Read More

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December 2020

Circular RNA CircMAP3K5 Acts as a MicroRNA-22-3p Sponge to Promote Resolution of Intimal Hyperplasia Via TET2-Mediated Smooth Muscle Cell Differentiation.

Circulation 2021 Jan 19;143(4):354-371. Epub 2020 Nov 19.

From the Institute of Pediatrics (Z.Z., L.X., J.Q., X.F., Y.L., K.L., Z.L., Y.B., W.H.T.), Guangzhou Women and Children's Medical Centre, Guangzhou Medical University, Guangdong, China.

Background: Aberrant expression of circular RNA contributes to human diseases. Circular RNAs regulate gene expression by sequestering specific microRNAs. In this study, we investigated whether circMAP3K5 (circular mitogen-activated protein kinase 5) could act as a competing endogenous microRNA-22-3p (miR-22-3p) sponge and regulate neointimal hyperplasia. Read More

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January 2021