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Science Signaling

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https://www.readbyqxmd.com/read/28074012/reduced-abundance-of-the-e3-ubiquitin-ligase-e6ap-contributes-to-decreased-expression-of-the-ink4-arf-locus-in-non-small-cell-lung-cancer
#1
Cristina Gamell, Twishi Gulati, Yaara Levav-Cohen, Richard J Young, Hongdo Do, Pat Pilling, Elena Takano, Neil Watkins, Stephen B Fox, Prudence Russell, Doron Ginsberg, Brendon J Monahan, Gavin Wright, Alex Dobrovic, Sue Haupt, Ben Solomon, Ygal Haupt
The tumor suppressor p16(INK4a), one protein encoded by the INK4/ARF locus, is frequently absent in multiple cancers, including non-small cell lung cancer (NSCLC). Whereas increased methylation of the encoding gene (CDKN2A) accounts for its loss in a third of patients, no molecular explanation exists for the remainder. We unraveled an alternative mechanism for the silencing of the INK4/ARF locus involving the E3 ubiquitin ligase and transcriptional cofactor E6AP (also known as UBE3A). We found that the expression of three tumor suppressor genes encoded in the INK4/ARF locus (p15(INK4b), p16(INK4a), and p19(ARF)) was decreased in E6AP(-/-) mouse embryo fibroblasts...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074011/new-connections-nherf-gates-activity
#2
Nancy R Gough
The NHERF molecular adaptors serve as gates for TRPC4 and TRPC5 regulation by diacylglycerol and recognition of CFTR by the quality control checkpoint.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074010/tumors-block-pain-with-cxcl12
#3
Nancy R Gough
The chemokine CXCL12 released from early stage pancreatic cancer recruits Schwann cells and suppresses pain signaling.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074009/papers-of-note-in-science-355-6320
#4
Annalisa M VanHook
This week's articles demonstrate that prostate cancer cells become resistant to androgen-deprivation therapy by changing their identity.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074008/papers-of-note-in-science-translational-medicine-9-371
#5
Leslie K Ferrarelli
This week's articles show that targeting the receptor PAR4 may be a safe antiplatelet agent and that a live cell-based therapy stimulates wound healing in leg ulcers.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074007/papers-of-note-in-nature-541-7635
#6
John F Foley
This week's articles show how targeting a fatty acid receptor blocks metastasis, reveal the structural basis for the mechanism of action of a potassium channel, and indicate that splicing factor 1 is required for life span extension in worms.
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074006/autocrine-wnt-regulates-the-survival-and-genomic-stability-of-embryonic-stem-cells
#7
Iris Augustin, Dyah L Dewi, Jennifer Hundshammer, Gerrit Erdmann, Grainne Kerr, Michael Boutros
Wnt signaling plays an important role in the self-renewal and differentiation of stem cells. The secretion of Wnt ligands requires Evi (also known as Wls). Genetically ablating Evi provides an experimental approach to studying the consequence of depleting all redundant Wnt proteins, and overexpressing Evi enables a nonspecific means of increasing Wnt signaling. We generated Evi-deficient and Evi-overexpressing mouse embryonic stem cells (ESCs) to analyze the role of autocrine Wnt production in self-renewal and differentiation...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074005/synergistic-regulation-of-serotonin-and-opioid-signaling-contributes-to-pain-insensitivity-in-nav1-7-knockout-mice
#8
Jörg Isensee, Leonhardt Krahé, Katharina Moeller, Vanessa Pereira, Jane E Sexton, Xiaohui Sun, Edward Emery, John N Wood, Tim Hucho
Genetic loss of the voltage-gated sodium channel Nav1.7 (Nav1.7(-/-)) results in lifelong insensitivity to pain in mice and humans. One underlying cause is an increase in the production of endogenous opioids in sensory neurons. We analyzed whether Nav1.7 deficiency altered nociceptive heterotrimeric guanine nucleotide-binding protein-coupled receptor (GPCR) signaling, such as initiated by GPCRs that respond to serotonin (pronociceptive) or opioids (antinociceptive), in sensory neurons. We found that the nociceptive neurons of Nav1...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28074004/signaling-by-two-component-system-noncognate-partners-promotes-intrinsic-tolerance-to-polymyxin-b-in-uropathogenic-escherichia-coli
#9
Kirsten R Guckes, Erin J Breland, Ellisa W Zhang, Sarah C Hanks, Navleen K Gill, Holly M S Algood, Jonathan E Schmitz, Charles W Stratton, Maria Hadjifrangiskou
Bacteria use two-component systems (TCSs) to react appropriately to environmental stimuli. Typical TCSs comprise a sensor histidine kinase that acts as a receptor coupled to a partner response regulator that coordinates changes in bacterial behavior, often through its activity as a transcriptional regulator. TCS interactions are typically confined to cognate pairs of histidine kinases and response regulators. We describe two distinct TCSs in uropathogenic Escherichia coli (UPEC) that interact to mediate a response to ferric iron...
January 10, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049772/placing-the-nuclear-pore-in-the-metformin-mechanism-of-action
#10
Nancy R Gough
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049771/a-dna-ribosylating-toxin-and-its-antidote
#11
Alexandra A Mushegian
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049770/papers-of-note-in-nature-540-7634
#12
Nancy R Gough
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049769/fasting-translation-control-and-seizures
#13
Leslie K Ferrarelli
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049768/papers-of-note-in-science-translational-medicine-8-370
#14
Leslie K Ferrarelli
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049767/papers-of-note-in-science-354-6319
#15
Annalisa M VanHook
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049766/nik-sends-mitochondria-to-the-periphery
#16
Annalisa M VanHook
No abstract text is available yet for this article.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049765/2016-signaling-breakthroughs-of-the-year
#17
EDITORIAL
Elizabeth M Adler
Signaling breakthroughs of 2016 clustered mainly in the areas of neuroscience, immunology, and metabolism, with excursions into plant hormone signaling and bacterial manipulation of host signaling pathways. Perhaps reflecting the growing maturity of the discipline of cell signaling, many of this year's breakthroughs have implications for the pathogenesis or treatment of human disease.
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049764/the-scf%C3%AE-trcp-e3-ubiquitin-ligase-complex-targets-lipin1-for-ubiquitination-and-degradation-to-promote-hepatic-lipogenesis
#18
Kouhei Shimizu, Hidefumi Fukushima, Kohei Ogura, Evan C Lien, Naoe Taira Nihira, Jinfang Zhang, Brian J North, Ailan Guo, Katsuyuki Nagashima, Tadashi Nakagawa, Seira Hoshikawa, Asami Watahiki, Koji Okabe, Aya Yamada, Alex Toker, John M Asara, Satoshi Fukumoto, Keiichi I Nakayama, Keiko Nakayama, Hiroyuki Inuzuka, Wenyi Wei
The SCF(β-TRCP) E3 ubiquitin ligase complex plays pivotal roles in normal cellular physiology and in pathophysiological conditions. Identification of β-transducin repeat-containing protein (β-TRCP) substrates is therefore critical to understand SCF(β-TRCP) biology and function. We used a β-TRCP-phosphodegron motif-specific antibody in a β-TRCP substrate screen coupled with tandem mass spectrometry and identified multiple β-TRCP substrates. One of these substrates was Lipin1, an enzyme and suppressor of the family of sterol regulatory element-binding protein (SREBP) transcription factors, which activate genes encoding lipogenic factors...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049763/the-receptor-tyrosine-kinase-axl-mediates-nuclear-translocation-of-the-epidermal-growth-factor-receptor
#19
Toni M Brand, Mari Iida, Kelsey L Corrigan, Cara M Braverman, John P Coan, Bailey G Flanigan, Andrew P Stein, Ravi Salgia, Jana Rolff, Randall J Kimple, Deric L Wheeler
The epidermal growth factor receptor (EGFR) is a therapeutic target in patients with various cancers. Unfortunately, resistance to EGFR-targeted therapeutics is common. Previous studies identified two mechanisms of resistance to the EGFR monoclonal antibody cetuximab. Nuclear translocation of EGFR bypasses the inhibitory effects of cetuximab, and the receptor tyrosine kinase AXL mediates cetuximab resistance by maintaining EGFR activation and downstream signaling. Thus, we hypothesized that AXL mediated the nuclear translocation of EGFR in the setting of cetuximab resistance...
January 3, 2017: Science Signaling
https://www.readbyqxmd.com/read/28049762/the-tyrosine-kinase-src-promotes-phosphorylation-of-the-kinase-tbk1-to-facilitate-type-i-interferon-production-after-viral-infection
#20
Xuelian Li, Mingjin Yang, Zhou Yu, Songqing Tang, Lei Wang, Xuetao Cao, Taoyong Chen
Various pattern recognition receptors (PRRs) are activated in response to viral infection to stimulate the production of type I interferons (IFNs). However, central to the responses of all of these receptors is their activation of the kinase TBK1, which stimulates transcription by IFN regulatory factor 3 (IRF3). We investigated the mechanism by which the kinase activity of TBK1 is stimulated in response to viral infection. We found that the tyrosine kinase Src promoted the phosphorylation of TBK1 on Tyr(179) upon viral infection of RAW264...
January 3, 2017: Science Signaling
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