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https://www.readbyqxmd.com/read/28077622/ciliary-entry-of-kif17-is-dependent-on-its-binding-to-the-ift-b-complex-via-ift46-ift56-as-well-as-on-its-nuclear-localization-signal
#1
Teruki Funabashi, Yohei Katoh, Saki Michisaka, Masaya Terada, Maho Sugawa, Kazuhisa Nakayama
Cilia function as cellular antennae to sense and transduce extracellular signals. A number of proteins are specifically localized in cilia. Anterograde and retrograde ciliary protein trafficking are mediated by the IFT-B and IFT-A complexes in concert with kinesin-2 and dynein-2 motors, respectively. However, the role of KIF17, a homodimeric kinesin-2 protein, in protein trafficking has not been fully understood in vertebrate cilia. In this study, we first demonstrated by taking advantage of the visible immunoprecipitation assay, that KIF17 interacts with the IFT46-IFT56 dimer in the IFT-B complex through its C-terminal sequence located immediately upstream of the nuclear localization signal (NLS)...
January 11, 2017: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/28075463/expression-of-the-promyelocytic-leukemia-protein-without-the-nuclear-localization-signal-as-a-novel-diagnostic-marker-for-acute-promyelocytic-leukemia
#2
Ting Xu, Xiao-Qun Yang, Kai-Ling Jiang, Hui Wang, Peng-Peng Ma, Liang Zhong, Bei-Zhong Liu
Promyelocytic leukemia-retinoic acid receptor α (PML-RARα) is a fusion protein generated by the t(15;17)(q22;q12) translocation associated with acute promyelocytic leukemia (APL). PML-RARα is cleaved by neutrophil elastase, an early myeloid-specific serine protease, leading to translocation of the nuclear localization signal (NLS) of the PML protein to the N-terminal of RARα, and the mutational product PML(NLS-). The present study was designed to analyze the role of the NLS in mediating PML transport into the nucleus and to evaluate the value of measuring NLS translocation in the early diagnosis of APL...
January 9, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28074610/an-in%C3%A2-vitro-model-yields-importin-new-insights-into-chronic-traumatic-encephalopathy-damaged-astrocytes-stop-thrombospondin-to-the-injury-an-editorial-highlight-for-defective-synthesis-and-release-of-astrocytic-thrombospondin-1-mediates-the-neuronal-tdp-43
#3
EDITORIAL
Sausan M Jaber, Brian M Polster
Read the highlighted article 'Defective synthesis and release of astrocytic thrombospondin-1 mediates the neuronal TDP-43 proteinopathy, resulting in defects in neuronal integrity associated with chronic traumatic encephalopathy: in vitro studies' on doi: 10.1111/jnc.13867.
January 10, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28071726/the-ppe2-protein-of-mycobacterium-tuberculosis-translocates-to-host-nucleus-and-inhibits-nitric-oxide-production
#4
Khalid Hussain Bhat, Shruti Srivastava, Sandeep Kumar Kotturu, Sudip Ghosh, Sangita Mukhopadhyay
Mycobacterium tuberculosis, the bacterium that causes tuberculosis, is one of the most successful pathogens of humans. It has evolved several adaptive skills and evasion mechanisms to hijack the immunologically educated host to suit its intracellular lifestyle. Here, we show that one of the unique PPE family member proteins of M. tuberculosis, PPE2, can limit nitric oxide (NO) production by inhibiting inos gene transcription. PPE2 protein has a leucine zipper DNA-binding motif and a functional nuclear localization signal...
January 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28054750/somatic-med12-nonsense-mutation-escapes-mrna-decay-and-reveals-a-motif-required-for-nuclear-entry
#5
Tuomas Heikkinen, Kati Kämpjärvi, Salla Keskitalo, Pernilla von Nandelstadh, Xiaonan Liu, Ville Rantanen, Esa Pitkänen, Matias Kinnunen, Heikki Kuusanmäki, Mika Kontro, Mikko Turunen, Netta Mäkinen, Jussi Taipale, Caroline Heckman, Kaisa Lehti, Satu Mustjoki, Markku Varjosalo, Pia Vahteristo
MED12 is a key component of the transcription-regulating Mediator complex. Specific missense and in-frame insertion/deletion mutations in exons 1 and 2 have been identified in uterine leiomyomas, breast tumors, and chronic lymphocytic leukemia. Here, we characterize the first MED12 5' end nonsense mutation (c.97G>T, p.E33X) identified in acute lymphoblastic leukemia and show that it escapes nonsense-mediated mRNA decay (NMD) by using an alternative translation initiation site. The resulting N-terminally truncated protein is unable to enter the nucleus due to the lack of identified nuclear localization signal (NLS)...
January 5, 2017: Human Mutation
https://www.readbyqxmd.com/read/28040778/latrunculin-a-induced-perturbation-of-the-actin-cytoskeleton-mediates-pap1p-dependent-induction-of-the-caf5p-efflux-pump-in-schizosaccharomyces-pombe
#6
Farzad Asadi, Bidhan Chakraborty, Jim Karagiannis
As part of an earlier study aimed at uncovering gene-products with roles in defending against latrunculin A (LatA) induced cytoskeletal perturbations, we identified three members of the oxidative stress response pathway: the Pap1p AP-1 like transcription factor, the Imp1p importin-alpha, and the Caf5p efflux pump. In this report, we characterize the pathway further and show that Pap1p translocates from the cytoplasm to the nucleus in an Imp1p-dependent manner upon LatA treatment. Moreover, preventing this translocation -- through the addition of a nuclear export signal - confers the same characteristic LatA-sensitive phenotype exhibited by pap1Δ cells...
December 30, 2016: G3: Genes—Genomes—Genetics
https://www.readbyqxmd.com/read/28040728/cytoplasmic-poly-ga-aggregates-impair-nuclear-import-of-tdp-43-in-c9orf72-als-ftld
#7
Bahram Khosravi, Hannelore Hartmann, Stephanie May, Christoph Möhl, Helena Ederle, Meike Michaelsen, Martin H Schludi, Dorothee Dormann, Dieter Edbauer
A repeat expansion in the non-coding region of C9orf72 gene is the most common mutation causing frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). Sense and antisense transcripts are translated into aggregating dipeptide repeat (DPR) proteins in all reading frames (poly-GA,-GP,-GR,-PA and -PR) through an unconventional mechanism. How these changes contribute to cytoplasmic mislocalization and aggregation of TDP-43 and thereby ultimately lead to neuron loss remains unclear. The repeat RNA itself and poly-GR/PR have been linked to impaired nucleocytoplasmic transport...
December 30, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/28031410/nuclear-import-of-jak1-is-mediated-by-a-classical-nls-and-is-required-for-survival-of-diffuse-large-b-cell-lymphoma
#8
Fen Zhu, Byounghoon Hwang, Shigeki Miyamoto, Lixin Rui
: Janus kinases (JAKs) are non-receptor tyrosine kinases that are generally found in association with cytokine receptors. In the canonical pathway, roles of JAKs have well been established in activating signal transducers and activators of transcription (STATs) in response to cytokine stimulation to modulate gene transcription. In contrast, a non-canonical role of JAK2 has recently been discovered in which JAK2 in the nucleus imparts the epigenetic regulation of gene transcription through phosphorylation of tyrosine 41 on the histone protein H3...
December 28, 2016: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27993670/interactome-of-the-inhibitory-isoform-of-the-nuclear-transporter-importin-13
#9
Shadma Fatima, Kylie M Wagstaff, Kim G Lieu, Rebecca G Davies, Satomi S Tanaka, Yasuka L Yamaguchi, Kate L Loveland, Patrick P L Tam, David A Jans
Importin 13 (Imp13) is a bidirectional nuclear transporter of proteins involved in a range of important cellular processes, with an N-terminally truncated inhibitory isoform (tImp13) specifically expressed in testis. To gain insight into tImp13 function, we performed a yeast-2-hybrid screen from a human testis cDNA library, identifying for the first time a suite of interactors with roles in diverse cellular process. We validated the interaction of tImp13 with Eukaryotic translation initiation factor 4γ2 (EIF4G2) and High mobility group containing protein 20A (HMG20A), benchmarking that with glucocorticoid receptor (GR), a known Imp13 interactor expressed in testis...
December 16, 2016: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27979731/nucleoporin-nup358-facilitates-nuclear-import-of-methoprene-tolerant-met-in-an-importin-%C3%AE-and-hsp83-dependent-manner
#10
Qianyu He, Yuanxi Zhang, Xu Zhang, DanDan Xu, Wentao Dong, Sheng Li, Rui Wu
The bHLH-PAS transcription factor, Methoprene-tolerant (Met)(1), functions as a juvenile hormone (JH) receptor and transduces JH signals by directly binding to E-box like motifs in the regulatory regions of JH response genes. Nuclear localization of Met is crucial for its transcriptional activity. Our previous studies have shown that the chaperone protein Hsp83 facilitates JH-induced Met nuclear import in Drosophila melanogaster. However, the exact molecular mechanisms of Met nuclear transport are not fully elucidated...
December 12, 2016: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/27956495/dna-polymerase-%C3%AE-contains-a-functional-nuclear-localization-signal-at-its-n-terminus
#11
Thomas W Kirby, Natalie R Gassman, Cassandra E Smith, Ming-Lang Zhao, Julie K Horton, Samuel H Wilson, Robert E London
DNA polymerase β (pol β) requires nuclear localization to fulfil its DNA repair function. Although its small size has been interpreted to imply the absence of a need for active nuclear import, sequence and structural analysis suggests that a monopartite nuclear localization signal (NLS) may reside in the N-terminal lyase domain. Binding of this domain to Importin α1 (Impα1) was confirmed by gel filtration and NMR studies. Affinity was quantified by fluorescence polarization analysis of a fluorescein-tagged peptide corresponding to pol β residues 2-13...
December 11, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27939291/structures-of-the-karyopherins-kap121p-and-kap60p-bound-to-the-nuclear-pore-targeting-domain-of-the-sumo-protease-ulp1p
#12
Hidemi Hirano, Junya Kobayashi, Yoshiyuki Matsuura
The budding yeast small ubiquitin-like modifier (SUMO) protease Ulp1p catalyzes both the processing of newly synthesized SUMO to its mature form and the deconjugation of SUMO from target proteins, thereby regulating a wide range of cellular processes including cell division, DNA repair, DNA replication, transcription, and mRNA quality control. Ulp1p is localized primarily at the nuclear pore complex (NPC) through interactions involving the karyopherins Kap121p and Kap95p-Kap60p heterodimer and a subset of nuclear pore-associated proteins...
December 6, 2016: Journal of Molecular Biology
https://www.readbyqxmd.com/read/27918136/development-of-cell-permeable-non-helical-constrained-peptides-to-target-a-key-protein-protein-interaction-in-ovarian-cancer
#13
Mareike M Wiedmann, Yaw Sing Tan, Yuteng Wu, Shintaro Aibara, Wenshu Xu, Hannah F Sore, Chandra S Verma, Laura Itzhaki, Murray Stewart, James D Brenton, David R Spring
There is a lack of current treatment options for ovarian clear cell carcinoma (CCC) and the cancer is often resistant to platinum-based chemotherapy. Hence there is an urgent need for novel therapeutics. The transcription factor hepatocyte nuclear factor 1β (HNF1β) is ubiquitously overexpressed in CCC and is seen as an attractive therapeutic target. This was validated through shRNA-mediated knockdown of the target protein, HNF1β, in five high- and low-HNF1β-expressing CCC lines. To inhibit the protein function, cell-permeable, non-helical constrained proteomimetics to target the HNF1β-importin α protein-protein interaction were designed, guided by X-ray crystallographic data and molecular dynamics simulations...
January 9, 2017: Angewandte Chemie
https://www.readbyqxmd.com/read/27902702/selective-inhibitor-of-nuclear-export-sine-compounds-alter-new-world-alphavirus-capsid-localization-and-reduce-viral-replication-in-mammalian-cells
#14
Lindsay Lundberg, Chelsea Pinkham, Cynthia de la Fuente, Ashwini Brahms, Nazly Shafagati, Kylie M Wagstaff, David A Jans, Sharon Tamir, Kylene Kehn-Hall
The capsid structural protein of the New World alphavirus, Venezuelan equine encephalitis virus (VEEV), interacts with the host nuclear transport proteins importin α/β1 and CRM1. Novel selective inhibitor of nuclear export (SINE) compounds, KPT-185, KPT-335 (verdinexor), and KPT-350, target the host's primary nuclear export protein, CRM1, in a manner similar to the archetypical inhibitor Leptomycin B. One major limitation of Leptomycin B is its irreversible binding to CRM1; which SINE compounds alleviate because they are slowly reversible...
November 2016: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/27866280/proteasome-mediated-degradation-of-tyrosine-hydroxylase-triggered-by-its-phosphorylation-a-new-question-as-to-the-intracellular-location-at-which-the-degradation-occurs
#15
REVIEW
Akira Nakashima, Yu Kodani, Yoko S Kaneko, Hiroshi Nagasaki, Akira Ota
Tyrosine hydroxylase (TH) is the rate-limiting enzyme in catecholamine biosynthesis, and its stability is a fundamental factor to maintain the level of the catecholamines in cells. However, the intracellular stability of TH determined by the degradation remains unknown; although the TH molecule phosphorylated at its Ser19 was observed in the nucleus, and the phosphorylation suspected to trigger its proteasome-mediated degradation. Computer-assisted analysis using the cNLS Mapper program predicted that two sequences of nuclear localization signals (NLS) exist in the N-terminus of TH molecule containing the phosphorylation sites Ser19, Ser31, and Ser40 (Pro(9)-Arg(38) and Lys(12)-Ile(42)): the NLS scores indicated that TH could become localized in both nucleus and cytoplasm...
November 19, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/27865090/characterization-of-the-subcellular-localization-and-nuclear-import-molecular-mechanisms-of-herpes-simplex-virus-1-ul2
#16
Mingsheng Cai, Zebin Huang, Zongmin Liao, Tao Chen, Ping Wang, Si Jiang, Daixiong Chen, Tao Peng, Yun Bian, Gengde Hong, Hang Yang, Zhancheng Zeng, Xiaowei Li, Meili Li
As a crucial protein, the herpes simplex virus 1 (HSV-1) UL2 protein has been shown to take part in various stages of viral infection, nonetheless, its exact subcellular localization and transport molecular determinants are not well known thus far. In the present study, by using live cells fluorescent microscopy assay, UL2 tagged with enhanced yellow fluorescent protein was transiently expressed in live cells and showed a completely nuclear accumulation without the presence of other HSV-1 proteins. Moreover, the nuclear transport of UL2 was characterized to be assisted by multiple transport pathways through Ran-, importin α1-, α5-, α7-, β1- and transportin-1 cellular transport receptors...
December 28, 2016: Biological Chemistry
https://www.readbyqxmd.com/read/27862840/differential-nucleocytoplasmic-shuttling-of-the-nucleoprotein-of-influenza-a-viruses-and-association-with-host-tropism
#17
Jing Li, Weinan Zheng, Lidan Hou, Can Chen, Wenhui Fan, Hongren Qu, Jingwen Jiang, Jinhua Liu, George F Gao, Jiyong Zhou, Lei Sun, Wenjun Liu
The nucleoprotein (NP) of influenza A virus plays a crucial role in virus replication, infectivity, and host adaptation. As a major component of the viral ribonucleoprotein complexes (vRNP), NP initiates vRNP shuttling between the nucleus and cytoplasm in the host cell. However, the characteristics of the nucleocytoplasmic shuttling of NP from H1N1 influenza A virus still remain unclear. In the present study, the subcellular localization and the related key residues of the H1N1 influenza virus NP were identified and evaluated...
November 8, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27847648/increases-in-retrograde-injury-signaling-complex-related-transcripts-in-central-axons-following-injury
#18
Gunja K Pathak, Hannah Ornstein, Helim Aranda-Espinoza, Amy J Karlsson, Sameer B Shah
Axons in the peripheral nervous system respond to injury by activating retrograde injury signaling (RIS) pathways, which promote local axonal protein synthesis (LPS) and neuronal regeneration. RIS is also initiated following injury of neurons in the central nervous system (CNS). However, regulation of the localization of axonal mRNA required for LPS is not well understood. We used a hippocampal explant system to probe the regulation of axonal levels of RIS-associated transcripts following axonal injury. Axonal levels of importin β1 and RanBP1 were elevated biphasically at 1 and 24 hrs after axotomy...
2016: Neural Plasticity
https://www.readbyqxmd.com/read/27835978/importins-promote-high-frequency-nf-%C3%AE%C2%BAb-oscillations-increasing-information-channel-capacity
#19
Zbigniew Korwek, Karolina Tudelska, Paweł Nałęcz-Jawecki, Maciej Czerkies, Wiktor Prus, Joanna Markiewicz, Marek Kochańczyk, Tomasz Lipniacki
BACKGROUND: Importins and exportins influence gene expression by enabling nucleocytoplasmic shuttling of transcription factors. A key transcription factor of innate immunity, NF-κB, is sequestered in the cytoplasm by its inhibitor, IκBα, which masks nuclear localization sequence of NF-κB. In response to TNFα or LPS, IκBα is degraded, which allows importins to bind NF-κB and shepherd it across nuclear pores. NF-κB nuclear activity is terminated when newly synthesized IκBα enters the nucleus, binds NF-κB and exportin which directs the complex to the cytoplasm...
November 11, 2016: Biology Direct
https://www.readbyqxmd.com/read/27819319/nuclear-import-of-dimerized-ribosomal-protein-rps3-in-complex-with-its-chaperone-yar1
#20
Valentin Mitterer, Nadine Gantenbein, Ruth Birner-Gruenberger, Guillaume Murat, Helmut Bergler, Dieter Kressler, Brigitte Pertschy
After their cytoplasmic synthesis, ribosomal proteins need to be transported into the nucleus, where they assemble with ribosomal RNA into pre-ribosomal particles. Due to their physicochemical properties, they need protection from aggregation on this path. Newly synthesized ribosomal protein Rps3 forms a dimer that is associated with one molecule of its specific chaperone Yar1. Here we report that redundant pathways contribute to the nuclear import of Rps3, with the classical importin α/β pathway (Kap60/Kap95 in yeast) constituting a main import route...
November 7, 2016: Scientific Reports
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