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Journal of Molecular Cell Biology

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https://read.qxmd.com/read/30779851/sequencing-the-landscape-of-cerebellar-gene-expression
#1
Ying Shen
No abstract text is available yet for this article.
February 19, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30753537/adam10-sheddase-activation-is-controlled-by-cell-membrane-asymmetry
#2
Florian Bleibaum, Anselm Sommer, Martin Veit, Björn Rabe, Jörg Andrä, Karl Kunzelmann, Christian Nehls, Wilmar Correa, Thomas Gutsmann, Joachim Grötzinger, Sucharit Bhakdi, Karina Reiss
Dysregulation of the disintegrin-metalloproteinase ADAM10 may contribute to the development of diseases including tumorigenesis and Alzheimer's disease. The mechanisms underlying ADAM10 sheddase activation are incompletely understood. Here, we show that transient exposure of the negatively charged phospholipid phosphatidylserine (PS) is necessarily required. The soluble PS headgroup was found to act as competitive inhibitor of substrate cleavage. Overexpression of the Ca2+-dependent phospholipid scramblase Anoctamin-6 (ANO6) led to increased PS externalization and substrate release...
February 12, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30753517/microrna-24-promotes-pancreatic-beta-cells-toward-dedifferentiation-to-avoid-endoplasmic-reticulum-stress-induced-apoptosis
#3
Yunxia Zhu, Yi Sun, Yuncai Zhou, Yan Zhang, Tao Zhang, Yating Li, Weiyan You, Xiaoai Chang, Li Yuan, Xiao Han
Current research indicates that beta cell loss in type 2 diabetes may be attributed to beta cell dedifferentiation rather than apoptosis; however, the mechanisms by which this occurs remain poorly understood. Our previous study demonstrated that elevation of microRNA-24 (miR-24) in a diabetic setting caused beta cell dysfunction and replicative deficiency. In this study, we focused on the role of miR-24 in beta cell apoptosis and dedifferentiation under endoplasmic reticulum (ER) stress conditions. We found that miR-24 overabundance protected beta cells from thapsigargin (TG)-induced apoptosis at the cost of accelerating the impairment of glucose-stimulated insulin secretion (GSIS) and enhancing the presence of dedifferentiation markers...
February 12, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30726988/numb-regulates-the-endocytosis-and-activity-of-the-anaplastic-lymphoma-kinase-in-an-isoform-specific-manner
#4
Ran Wei, Xuguang Liu, Courtney Voss, Wentao Qin, Lina Dagnino, Lei Li, Marc Vigny, Shawn Shun-Cheng Li
NUMB is an evolutionarily conserved protein that plays an important role in cell adhesion, migration, polarity, and cell fate determination. It has also been shown to play a role in the pathogenesis of certain cancers, although it remains controversial whether NUMB functions as an oncoprotein or tumor suppressor. Here, we show that NUMB binds to anaplastic lymphoma kinase (ALK), a receptor tyrosine kinase aberrantly activated in several forms of cancer, and this interaction regulates the endocytosis and activity of ALK...
February 6, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30726932/glucocorticoid-receptor-irs-1-axis-controls-emt-and-the-metastasis-of-breast-cancers
#5
Weiwei Shi, Dongmei Wang, Xinwang Yuan, Yi Liu, Xiaojie Guo, Jingsong Li, Jian-Guo Song
Glucocorticoid receptor (GR) is involved in the transcriptional regulation of genes that are important for various biological functions, including tumor growth and metastatic progression. However, the cellular and biological effects of GR remain poorly understood. Here, we investigated the role of GR and its underlying mechanism in mediating breast cancer cell survival and metastasis. We observed that the GR levels were increased in drug-resistant breast cancer cells and in metastatic breast cancer samples...
February 6, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30726928/roles-of-computational-modelling-in-understanding-p53-structure-biology-and-its-therapeutic-targeting
#6
Yaw Sing Tan, Yasmina Mhoumadi, Chandra S Verma
The multi-faceted role of the transcription factor p53 is key to numerous biological processes, including the suppression of tumours. The availability since the 1990s of a richness of biophysical data aimed at understanding its structure-function relationships has enabled the application of a variety of atomistic computational modelling techniques towards the establishment of mechanistic models. Together they have provided deep insights into the structure, mechanics, energetics, and dynamics of p53. In parallel, the observation that mutations in p53 or changes in its associated pathways characterise several human cancers has resulted in a race to develop therapeutic modulators of p53, some of which have entered clinical trials...
February 6, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30698724/morphine-induces-dysfunction-of-pink1-parkin-mediated-mitophagy-in-spinal-cord-neurons-implying-involvement-in-antinociceptive-tolerance
#7
Hong Kong, Chun-Yi Jiang, Liang Hu, Peng Teng, Yan Zhang, Xiu-Xiu Pan, Xiao-Di Sun, Wen-Tao Liu
The development of opioid-induced analgesic tolerance is a clinical challenge in long-term use for managing chronic pain. The mechanisms of morphine tolerance are poorly understood. Mitochondria-derived reactive oxygen species (ROS) is a crucial signal inducing analgesic tolerance and pain. Chronic administration of morphine leads to robust ROS production and accumulation of damaged mitochondria, which are immediately removed by mitophagy. Here, we show that morphine inhibits mitochondria damage-induced accumulation of PTEN-induced putative kinase 1 (PINK1) in neurons...
January 30, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30690467/single-cell-transcriptomes-reveal-molecular-specializations-of-neuronal-cell-types-in-the-developing-cerebellum
#8
Jian Peng, Ai-Li Sheng, Qi Xiao, Libing Shen, Xiang-Chun Ju, Min Zhang, Si-Ting He, Chao Wu, Zhen-Ge Luo
The cerebellum is critical for controlling motor and non-motor functions via cerebellar circuit that is composed of defined cell types, which approximately account for more than half of neurons in mammals. The molecular mechanisms controlling developmental progression and maturation processes of various cerebellar cell types need systematic investigation. Here, we analyzed transcriptome profiles of 21119 single cells of the postnatal mouse cerebellum and identified eight main cell clusters. Functional annotation of differentially expressed genes revealed trajectory hierarchies of granule cells (GCs) at various states and implied roles of mitochondrion and ATPases in the maturation of Purkinje cells (PCs), the sole output cells of the cerebellar cortex...
January 25, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30689920/the-long-and-the-short-of-it-the-mdm4-tail-so-far
#9
Sue Haupt, Octavio Mejia Hernandez, Reshma Vijayakumaran, Simon Keam, Ygal Haupt
The mouse double minute 4 (MDM4) is emerging from the shadow of its more famous relative MDM2 and is starting to steal the limelight, largely due to its therapeutic possibilities. MDM4 is a vital regulator of the tumour suppressor p53. It restricts p53 transcriptional activity and also, at least in development, facilitates MDM2's E3 ligase activity toward p53. These functions of MDM4 are critical for normal cell function and a proper response to stress. Their importance for proper cell maintenance and proliferation identifies them as a risk for deregulation associated with the uncontrolled growth of cancer...
January 25, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30689917/small-molecule-activators-of-the-p53-response
#10
Marcus J G W Ladds, Sonia Laín
Drugging the p53 pathway has been a goal for both academics and pharmaceutical companies since the designation of p53 as the 'guardian of the genome'. Through growing understanding of p53 biology, we can see multiple routes for activation of both wild-type p53 function and restoration of mutant p53. In this review, we focus on small molecules that activate wild-type p53 and that do so in a non-genotoxic manner. In particular, we will describe potential approaches to targeting proteins that alter p53 stability and function through posttranslational modification, affect p53's subcellular localization, or target RNA synthesis or the synthesis of ribonucleotides...
January 25, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30629198/aff3-a-new-player-in-maintaining-xist-monoallelic-expression
#11
Reiner A Veitia
No abstract text is available yet for this article.
January 10, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30629188/conversion-of-mouse-fibroblasts-into-oligodendrocyte-progenitor-like-cells-through-a-chemical-approach
#12
Chang Liu, Xu Hu, Yawen Li, Wenjie Lu, Wenlin Li, Nan Cao, Saiyong Zhu, Jinke Cheng, Sheng Ding, Mingliang Zhang
Transplantation of oligodendrocyte progenitor cells (OPCs) is a promising way for treating demyelinating diseases. However, generation of scalable and autologous sources of OPCs has proven difficult. We previously established a chemical condition M9 that could specifically initiate neural program in mouse embryonic fibroblasts. Here we found that M9 could induce the formation of colonies that undergo mesenchymal-to-epithelial transition at the early stage of reprogramming. These colonies may represent unstable and neural lineage-restricted intermediates that have not established a neural stem cell identity...
January 10, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30624728/the-role-of-p53-in-developmental-syndromes
#13
Margot E Bowen, Laura D Attardi
While it is well appreciated that loss of the p53 tumor suppressor protein promotes cancer, growing evidence indicates that increased p53 activity underlies the developmental defects in a wide range of genetic syndromes. The inherited or de novo mutations that cause these syndromes affect diverse cellular processes, such as ribosome biogenesis, DNA repair, and centriole duplication, and analysis of human patient samples and mouse models demonstrates that disrupting these cellular processes can activate the p53 pathway...
January 8, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30624687/resident-prrx1-lineage-stromal-cells-promote-t-cell-survival-in-the-spleen
#14
Wanyao Zhang, Qian Yu, Huijuan Liu, Baojie Li
No abstract text is available yet for this article.
January 8, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30608603/it-takes-a-team-a-gain-of-function-story-of-p53-r249s
#15
Huai Wang, Peng Liao, Shelya X Zeng, Hua Lu
Gain of function (GOF), the most malicious oncogenic activity of a cancer-promoting protein, is well illustrated to three hot spot p53 mutations at R248, R175, and R273 with distinct molecular mechanisms. Yet, less is known about another hot spot p53 mutant, R249S (p53-R249S). p53-R249S is the sole hot spot mutation in hepatocellular carcinoma (HCC) that is highly associated with chronic hepatitis B virus (HBV) infection and dietary exposure to aflatoxin B1 (AFB1). Its GOF is suggested by the facts that this mutant is associated with earlier onset of HCC and poorer prognosis of cancer patients and that its overexpression drives HCC proliferation and tumorigenesis...
January 4, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30605539/news-about-non-secretory-exocytosis-mechanisms-properties-and-functions
#16
Rosalba D'Alessandro, Jacopo Meldolesi
The fusion by exocytosis of many vesicles to the plasma membrane induces the discharge to the extracellular space of their abundant luminal cargoes. Other exocytic vesicles, however, do not contain cargoes, and thus, their fusion is not followed by secretion. Therefore, two distinct processes of exocytosis exist, one secretory and the other non-secretory. The present review deals with the knowledge of non-secretory exocytosis developed during recent years. Among such developments are the dual generation of the exocytic vesicles, initially released either from the trans-Golgi network or by endocytosis; their traffic with activation of receptors, channels, pumps, and transporters; the identification of their tethering and Soluble N-ethylmaleimide-sensitive factor Attachment protein REceptor complexes that govern membrane fusions; the growth of axons and the membrane repair...
January 3, 2019: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30590706/dcaf1-vprbp-emerging-physiological-roles-for-a-unique-dual-service-e3-ubiquitin-ligase-substrate-receptor
#17
N Max Schabla, Koushik Mondal, Patrick C Swanson
Cullin-RING ligases (CRLs) comprise a large group of modular eukaryotic E3 ubiquitin ligases. Within this family, the CRL4 ligase (consisting of the Cullin4 [CUL4] scaffold protein, the Rbx1 RING finger domain protein, the damaged DNA binding protein 1 [DDB1], and one of many DDB1-associated substrate receptor proteins) has been intensively studied in recent years due to its involvement in regulating various cellular processes, its role in cancer development and progression, and its subversion by viral accessory proteins...
December 24, 2018: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30561692/nuclear-actin-switch-of-the-ino80-remodeler
#18
Jun Wu, Yimin Lao, Bing Li
No abstract text is available yet for this article.
December 18, 2018: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30535344/functional-relationship-between-p53-and-runx-proteins
#19
Suk-Chul Bae, Arun Mouli Kolinjivadi, Yoshiaki Ito
RUNX genes belong to a three-membered family of transcription factors, which are well established as master regulators of development. Of them, aberrations in RUNX3 expression are frequently observed in human malignancies primarily due to epigenetic silencing which is often overlooked. At the G1 phase of the cell cycle, RUNX3 regulates the restriction (R)-point, a mechanism that decides cell cycle entry. Deregulation at the R-point or loss of RUNX3 results in premature entry into S phase, leading to a proliferative advantage...
December 11, 2018: Journal of Molecular Cell Biology
https://read.qxmd.com/read/30535390/aff3-dna-methylation-interplay-in-maintaining-the-mono-allelic-expression-pattern-of-xist-in-terminally-differentiated-cells
#20
Yue Zhang, Chao Wang, Xiaoxu Liu, Qian Yang, Hongliang Ji, Mengjun Yang, Manman Xu, Yunyan Zhou, Wei Xie, Zhuojuan Luo, Chengqi Lin
X chromosome inactivation and genomic imprinting are two classic epigenetic regulatory processes that cause mono-allelic gene expression. In female mammals, mono-allelic expression of the long non-coding RNA gene X-Inactive Specific Transcript (XIST) is essential for initiation of X chromosome inactivation upon differentiation. We have previously demonstrated that the central factor of super elongation complex-like 3 (SEC-L3), AFF3, is enriched at gamete differentially methylated regions (DMRs) of the imprinted loci and regulates the imprinted gene expression...
December 7, 2018: Journal of Molecular Cell Biology
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