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Journal of Molecular Cell Biology

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https://www.readbyqxmd.com/read/28077607/anatomy-of-mdm2-and-mdm4-in-evolution
#1
REVIEW
Ban Xiong Tan, Hoe Peng Liew, Joy S Chua, Farid J Ghadessy, Yaw Sing Tan, David P Lane, Cynthia R Coffill
Mouse double minute (Mdm) genes span an evolutionary timeframe from the ancient eukaryotic placozoa Trichoplax adhaerens to Homo sapiens, implying a significant and possibly conserved cellular role throughout history. Maintenance of DNA integrity and response to DNA damage involve many key regulatory pathways, including precise control over the tumour suppressor protein p53. In most vertebrates, degradation of p53 through proteasomal targeting is primarily mediated by heterodimers of Mdm2 and the Mdm2-related protein Mdm4 (also known as MdmX)...
January 10, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/28069666/negative-auto-regulators-trap-p53-in-their-web
#2
REVIEW
Xiang Zhou, Bo Cao, Hua Lu
The transcriptional factor p53 activates the expression of a myriad of target genes involving a complicated signaling network, resulting in various cellular outcomes, such as growth arrest, senescence, apoptosis, and metabolic changes, and leading to consequent suppression of tumor growth and progression. Because of the profoundly adverse effect of p53 on growth and proliferation of cancer cells, several feedback mechanisms have been employed by the cells to constrain p53 activity. Two major antagonists MDM2 and MDMX (the long forms) are transcriptionally induced by p53, but in return block p53 activity, forming a negative feedback circuit and rendering chemoresistance of several cancer cells...
January 9, 2017: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27932485/axonal-micrornas-localization-function-and-regulatory-mechanism-during-axon-development
#3
REVIEW
Bin Wang, Lan Bao
Subcellular localization and translation of messenger RNAs are essential for the regulation of neuronal development and synaptic function. As post-transcriptional regulators, microRNAs (miRNAs) have been emerging as central players in the development and maturation of the nervous system. Recent discoveries reveal the critical functions of miRNAs in the axon of neurons via multiple pathways of molecular regulation. Here, we introduce methods for isolating axonal miRNAs and review recent findings on the localization and function as well as regulatory mechanism of axonal miRNAs during axon development...
December 8, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27932484/role-of-mdm2-and-mdmx-in-dna-repair
#4
REVIEW
Christine M Eischen
Mdm2 and Mdmx are critical regulators of the p53 tumour suppressor and are overexpressed in many human malignancies. However, in recent years, their impact on genome instability was shown to be at least, in part, independent of p53. Both Mdm2 and Mdmx inhibit DNA break repair through their association with the Mre11/Rad50/Nbs1 DNA repair complex. Recent evidence indicates that harnessing Mdm2 and/or Mdmx-mediated inhibition of DNA break repair in cancer cells could provide a therapeutic opportunity, particularly for those malignancies that have lost functional p53...
December 8, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27932483/roles-and-regulations-of-the-ets-transcription-factor-elf4-mef
#5
REVIEW
Mary Ann Suico, Tsuyoshi Shuto, Hirofumi Kai
Most E26 transformation-specific (ETS) transcription factors are involved in the pathogenesis and progression of cancer. This is in part due to the roles of ETS transcription factors in basic biological processes such as growth, proliferation, and differentiation, and also because of their regulatory functions that have physiological relevance in tumorigenesis, immunity, and basal cellular homoeostasis. A member of the E74-like factor (ELF) subfamily of the ETS transcription factor family-myeloid elf-1-like factor (MEF), designated as ELF4-has been shown to be critically involved in immune response and signalling, osteogenesis, adipogenesis, cancer, and stem cell quiescence...
December 8, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927749/modulation-of-the-p53-mdm2-interplay-by-hausp-inhibitors
#6
REVIEW
Omid Tavana, Wei Gu
It is well established that both p53 and MDM2 are short-lived proteins whose stabilities are tightly controlled through ubiquitination-mediated degradation. Although numerous studies indicate that the MDM2 E3 ligase activity, as well as the protein-protein interaction between p53 and MDM2, is the major focus for this regulation, emerging evidence suggests that the deubiquitinase herpesvirus-associated ubiquitin-specific protease (HAUSP, also known as USP7) plays a critical role. Furthermore, HAUSP inhibition elevates p53 stability and might be beneficial for therapeutic purposes...
December 6, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27913571/snord126-promotes-hcc-and-crc-cell-growth-by-activating-the-pi3k-akt-pathway-through-fgfr2
#7
Xianlong Fang, Dongmei Yang, Hongping Luo, Shuai Wu, Wenjie Dong, Jing Xiao, Sujing Yuan, Aimin Ni, Kang-Jian Zhang, Xin-Yuan Liu, Liang Chu
Small nucleolar RNA (snoRNA) dysfunctions have been associated with cancer development. SNORD126 is an orphan C/D box snoRNA that is encoded within introns 5-6 of its host gene, cyclin B1-interacting protein 1 (CCNB1IP1) The cancer-associated molecular mechanisms triggered by SNORD126 are not fully understood. Here, we demonstrate that SNORD126 is highly expressed in hepatocellular carcinoma (HCC) and colorectal cancer (CRC) patient samples. SNORD126 increased Huh-7 and SW480 cell growth and tumorigenicity in nude mice...
December 2, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927750/mdm2-as-a-chromatin-modifier
#8
REVIEW
Magdalena Wienken, Ute M Moll, Matthias Dobbelstein
Mdm2 is the key negative regulator of the tumour suppressor p53, making it an attractive target for anti-cancer drug design. We recently identified a new role of Mdm2 in gene repression through its direct interaction with several proteins of the polycomb group (PcG) family. PcG proteins form polycomb repressive complexes PRC1 and PRC2. PRC2 (via EZH2) mediates histone 3 lysine 27 (H3K27) trimethylation, and PRC1 (via RING1B) mediates histone 2A lysine 119 (H2AK119) monoubiquitination. Both PRCs mostly support a compact and transcriptionally silent chromatin structure...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27927748/axl-receptor-signalling-suppresses-p53-in-melanoma-through-stabilization-of-the-mdmx-mdm2-complex
#9
Anna de Polo, Zhongling Luo, Casimiro Gerarduzzi, Xiang Chen, John B Little, Zhi-Min Yuan
Deregulation of the tyrosine kinase signalling is often associated with tumour progression and drug resistance, but its underlying mechanisms are only partly understood. In this study, we investigated the effects of the receptor tyrosine kinase AXL on the stability of the MDMX-MDM2 heterocomplex and the activity of p53 in melanoma cells. Our data demonstrated that AXL overexpression or activation through growth arrest-specific 6 (Gas6) ligand stimulation increases MDMX and MDM2 protein levels and decreases p53 activity...
November 9, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27856769/new-insights-into-complex-diseases
#10
EDITORIAL
Jiarui Wu
No abstract text is available yet for this article.
December 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27436752/prostaglandin-e2-receptor-ep3-regulates-both-adipogenesis-and-lipolysis-in-mouse-white-adipose-tissue
#11
Hu Xu, Jia-Lin Fu, Yi-Fei Miao, Chun-Jiong Wang, Qi-Fei Han, Sha Li, Shi-Zheng Huang, Sheng-Nan Du, Yu-Xiang Qiu, Ji-Chun Yang, Jan-Åke Gustafsson, Richard M Breyer, Feng Zheng, Nan-Ping Wang, Xiao-Yan Zhang, You-Fei Guan
Among the four prostaglandin E2 receptors, EP3 receptor is the one most abundantly expressed in white adipose tissue (WAT). The mouse EP3 gene gives rise to three isoforms, namely EP3α, EP3β, and EP3γ, which differ only at their C-terminal tails. To date, functions of EP3 receptor and its isoforms in WAT remain incompletely characterized. In this study, we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice. Genetic ablation of three EP3 receptor isoforms (EP3(-/-) mice) or EP3α and EP3γ isoforms with EP3β intact (EP3β mice) led to an obese phenotype with increased food intake, decreased motor activity, reduced insulin sensitivity, and elevated serum triglycerides...
December 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27190311/a-camp-and-creb-mediated-feed-forward-mechanism-regulates-gsk3%C3%AE-in-polycystic-kidney-disease
#12
Vijayakumar R Kakade, Shixin Tao, Madhumitha Rajagopal, Xia Zhou, Xiaogang Li, Alan S L Yu, James P Calvet, Pankaj Pandey, Reena Rao
Glycogen synthase kinase 3β (GSK3β), a serine/threonine protein kinase, is commonly known to be regulated at the level of its activity. However, in some diseases including polycystic kidney disease (PKD), GSK3β expression is increased and plays a pathophysiological role. The current studies aimed to determine the mechanism for the increased GSK3β expression in PKD and its significance to disease progression. In mouse models of PKD, increases in renal GSK3β corresponded with increases in renal cAMP levels and disease progression...
December 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27744377/comparative-population-genomics-reveals-genetic-basis-underlying-body-size-of-domestic-chickens
#13
Ming-Shan Wang, Yong-Xia Huo, Yan Li, Newton O Otecko, Ling-Yan Su, Hai-Bo Xu, Shi-Fang Wu, Min-Sheng Peng, He-Qun Liu, Lin Zeng, David M Irwin, Yong-Gang Yao, Dong-Dong Wu, Ya-Ping Zhang
Body size is the most important economic trait for animal production and breeding. Several hundreds of loci have been reported to be associated with growth trait and body weight in chickens. The loci are mapped to large genomic regions due to the low density and limited number of genetic markers in previous studies. Herein, we employed comparative population genomics to identify genetic basis underlying the small body size of Yuanbao chicken (a famous ornamental chicken) based on 89 whole genomes. The most significant signal was mapped to the BMP10 gene, whose expression was upregulated in the Yuanbao chicken...
October 15, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27744376/ampk-activation-by-peri-sciatic-nerve-administration-of-ozone-attenuates-cci-induced-neuropathic-pain-in-rats
#14
Lijuan Lu, Cailong Pan, Lu Chen, Liang Hu, Chaoyu Wang, Yuan Han, Yanjing Yang, Zhixiang Cheng, Wen-Tao Liu
Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. Ozone is widely used as an alternative therapy for many different pain conditions, with exact mechanisms still elusive. In this study, we found that a single peri-sciatic nerve injection of ozone decreased mechanical allodynia and thermal hyperalgesia, and normalized the phosphorylation of protein kinase C γ, N-methyl-D-aspartate receptor, and extracellular signal-regulated kinase in a chronic constriction injury (CCI) model in rat sciatic nerve...
October 15, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27702761/senp1-regulates-ifn-%C3%AE-stat1-signaling-through-stat3-socs3-negative-feedback-loop
#15
Tingting Yu, Yong Zuo, Rong Cai, Xian Huang, Shuai Wu, Chenxi Zhang, Y Eugene Chin, Dongdong Li, Zhenning Zhang, Nansong Xia, Qi Wang, Hao Shen, Xuebiao Yao, Zhong-Yin Zhang, Song Xue, Lei Shen, Jinke Cheng
Interferon-γ (IFN-γ) triggers macrophage for inflammation response by activating the intracellular JAK-STAT1 signaling. SOCS1 and protein tyrosine phosphatases can negatively modulate IFN-γ signaling. Here we identify a novel negative feedback loop mediated by STAT3-SOCS3, which is tightly controlled by SENP1 via de-SUMOylation of protein tyrosine phosphatase 1B (PTP1B), in IFN-γ signaling. SENP1-deficient macrophages show defects in IFN-γ signaling and M1 macrophage activation. PTP1B in SENP1-deficient macrophages is highly SUMOylated, which reduces PTP1B-induced de-phosphorylation of STAT3...
October 4, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27702760/bidirectional-regulation-of-fragile-x-mental-retardation-protein-phosphorylation-controls-rhodopsin-homeostasis
#16
Xiao Wang, Yawen Mu, Mengshi Sun, Junhai Han
Homeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how translation of Rh1 is regulated. Here, we show that adult photoreceptors maintain a constant, abundant quantity of ninaE mRNA, which encodes Rh1. We demonstrate that the Fmr1 protein associates with ninaE mRNA and represses its translation...
October 4, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27671445/adipocyte-derived-microvesicles-from-obese-mice-induce-m1-macrophage-phenotype-through-secreted-mir-155
#17
Yaqin Zhang, Hongliang Mei, Xiaoai Chang, Fang Chen, Yunxia Zhu, Xiao Han
The pro-inflammatory profile of M1 macrophage accumulation in adipose tissue is a central event leading to the metabolic complications of obesity. However, the mechanisms by which M1 macrophages are enriched in adipose tissue during weight gain remain incompletely understood. Here, we investigated the effects of adipocyte-derived microvesicles (ADM) on modulating macrophage phenotype in mice and explored the involved molecular signalling pathways. We found that, compared with ADM from lean mice (SD ADM), ADM from obese mice (HFD ADM) significantly enhanced M1 marker expression...
September 25, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27651430/tip60-inhibits-metastasis-by-ablating-dnmt1-snail2-driven-epithelial-mesenchymal-transition-program
#18
Yanzhou Zhang, Vanitha Krishna Subbaiah, Deepa Rajagopalan, Cheng Yong Tham, Lissa Nurrul Abdullah, Tan Boon Toh, Min Gong, Tuan Zea Tan, Shweta Pradip Jadhav, Amit Kumar Pandey, Neerja Karnani, Edward Kai-Hua Chow, Jean Paul Thiery, Sudhakar Jha
HIV-Tat-interacting protein of 60 kDa (TIP60) is a lysine acetyltransferase and known to be downregulated in multiple cancers. Among various signalling pathways, TIP60 is implicated in regulating epithelial-mesenchymal transition (EMT). Here, we show that TIP60 expression abrogates cell migration and metastatic potential of breast cancer cells using in vitro and in vivo models. Mechanistically, we show that this is through its ability to destabilize DNMT1 and inhibit SNAIL2 function (SNAIL2-mediated EMT/cell migration)...
September 20, 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27489305/progresses-in-developmental-biology
#19
EDITORIAL
Jiarui Wu
No abstract text is available yet for this article.
August 2016: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/27436754/the-b-cell-receptor-br3-modulates-cellular-branching-via-rac1-during-neuronal-migration
#20
LETTER
Lei Zhang, Feng Zhang, Tao Yang, Xizhou Zhu, Nuoyan Zheng, Hui Li, Desheng Zhu, Yan Zhu, Zhiheng Xu
No abstract text is available yet for this article.
August 2016: Journal of Molecular Cell Biology
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