Article
Biochemistry & Molecular Biology
Yoshiyuki Matsuura, Kazuya Miyawaki
Summary: HIF-1 is a transcription factor that regulates oxygen homeostasis by controlling its nuclear localization. The nuclear import of HIF-1a requires a specific nuclear localization signal, and its deletion leads to an almost complete loss of nuclear localization.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Gang Chen, Danyun Xu, Qing Liu, Zhichuang Yue, Biao Dai, Shujuan Pan, Yongqiang Chen, Xinhua Feng, Honghong Hu
Summary: The nuclear import of FLC during floral transition is mediated by the NUP62-subcomplex, which includes nucleoporins NUP62, NUP58, and NUP54, in an importin & alpha;-independent manner. The carrier protein SAD2 is critical for FLC nuclear import and flower transition mainly through the NUP62-subcomplex, which mediates the import of cargos with unconventional NLSs, including FLC.
JOURNAL OF INTEGRATIVE PLANT BIOLOGY
(2023)
Article
Biology
Alonso Javier Pardal, Andrew James Bowman
Summary: This study identified importin-5 as the major importin associated with cytoplasmic H3, which transfers its monomeric cargo to nuclear sNASP. Additionally, monomeric H4 interacts specifically with HAT1 and RBBP7. It was found that Imp5 and sNASP compete for binding H3, suggesting a direct interaction site competition requiring GTP-bound Ran for histone transfer.
Article
Biochemistry & Molecular Biology
Athanasios A. Panagiotopoulos, Chara Polioudaki, Sotirios G. Ntallis, Dimitris Dellis, George Notas, Christos A. Panagiotidis, Panayiotis A. Theodoropoulos, Elias Castanas, Marilena Kampa
Summary: The study identified a novel NLS signal sequence for importin 7 recognition using unsupervised computational methods and experimental validation, showcasing its effectiveness in breast cancer cells. Furthermore, it was found that importin 7-mediated nuclear protein transport is affected by cargo protein phosphorylation.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Article
Biochemistry & Molecular Biology
Andreas Steiner, Sebastien Favre, Maximilian Mack, Annika Hausharter, Benjamin Pillet, Jutta Hafner, Valentin Mitterer, Dieter Kressler, Brigitte Pertschy, Ingrid Zierler
Summary: The ribosome is assembled in the nucleus, and newly synthesized ribosomal proteins need to travel from the cytoplasm into the nucleus. This study reveals two mechanisms by which the small subunit ribosomal protein Rps2 is imported into the nucleus, involving an internal region (amino acids 76-145) and an N-terminal region (amino acids 10-28), which interact with importin-β Pse1 and Tsr4, respectively. This study uncovers new nuclear import signals for ribosomal proteins, demonstrating the versatility of the mechanisms coordinating their nuclear import.
Review
Plant Sciences
Feng Xiong, Edwin P. Groot, Yan Zhang, Sha Li
Summary: In eukaryotic cells, nuclear activities are isolated by the nuclear envelope, leading to the evolution of a highly conserved nuclear transport machinery, with the importin beta family playing a crucial role. This review summarizes the biological functions of importin beta family members in plants, including development, reproduction, stress responses, and immunity, highlighting new molecular functions such as protein turnover, miRNA regulation, and signaling. It provides a comprehensive view of this versatile protein family in plants.
JOURNAL OF EXPERIMENTAL BOTANY
(2021)
Article
Fisheries
Wenxing Li, Gejie Zhao, Zhiyuan Jiao, Chao Xiang, Ying Liang, Wenshu Huang, Pin Nie, Bei Huang
Summary: A new fish interferon regulatory factor, IRF11, has been found to have antiviral properties that require its nuclear entry and DNA binding. The orthologs of IRF11 have been identified in lamprey and lancelet species, suggesting an ancient origin of this gene. Further characterization of the IRF11 gene in the Japanese eel revealed its antiviral activities and the involvement of specific residues in DNA binding and activation of the interferon promoter.
DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY
(2023)
Article
Medicine, Research & Experimental
Wenjing Wang, Yoichi Miyamoto, Biaobang Chen, Juanzi Shi, Feiyang Diao, Wei Zheng, Qun Li, Lan Yu, Lin Li, Yao Xu, Ling Wu, Xiaoyan Mao, Jing Fu, Bin Li, Zheng Yan, Rong Shi, Xia Xue, Jian Mu, Zhihua Zhang, Tianyu Wu, Lin Zhao, Weijie Wang, Zhou Zhou, Jie Dong, Qiaoli Li, Li Jin, Lin He, Xiaoxi Sun, Ge Lin, Yanping Kuang, Lei Wang, Qing Sang
Summary: By analyzing whole-exome sequencing data of 606 women with PREMBA, researchers have identified a candidate gene KPNA7, which may contribute to the development of PREMBA. The study further revealed that KPNA7 mutations reduce protein levels, impair its binding capacity to substrate RSL1D1, and affect nuclear transport activity. Furthermore, the study found that mouse KPNA2 plays a critical role in embryonic development and its deficiency leads to embryo arrest, similar to human PREMBA cases. These findings provide a mechanistic understanding of PREMBA and a diagnostic marker for PREMBA patients.
JOURNAL OF CLINICAL INVESTIGATION
(2023)
Article
Oncology
Aderonke Ajayi-Smith, Pauline van der Watt, Nonkululeko Mkwanazi, Sarah Carden, John O. Trent, Virna D. Leaner
Summary: The study demonstrated that INI-60 has inhibitory effects on cancer cells while minimally affecting non-cancer cells, making it a potential anti-cancer agent. INI-60 alters the nuclear import activities of Kpn beta 1 and interferes with cancer cell biology, leading to apoptosis in cancer cells.
EXPERIMENTAL CELL RESEARCH
(2021)
Article
Multidisciplinary Sciences
Julia Kornienko, Marta Rodriguez-Martinez, Kai Fenzl, Florian Hinze, Daniel Schraivogel, Markus Grosch, Brigit Tunaj, Dominik Lindenhofer, Laura Schraft, Moritz Kueblbeck, Eric Smith, Chad Mao, Emily Brown, Anjali Owens, Ardan M. M. Saguner, Benjamin Meder, Victoria Parikh, Michael Gotthardt, Lars M. M. Steinmetz
Summary: The authors demonstrate that loss of interaction with the nuclear importer TNPO3 leads to cytoplasmic mislocalization of RBM20 variants associated with severe dilated cardiomyopathy. Restoring their nuclear localization can alleviate the disease phenotype. These findings provide insight into the molecular mechanism of RBM20 mislocalization and its role in dilated cardiomyopathy.
NATURE COMMUNICATIONS
(2023)
Article
Plant Sciences
Daniel Luedke, Charlotte Roth, Sieglinde A. Kamrad, Jana Messerschmidt, Denise Hartken, Jonas Appel, Bojan F. Hoernich, Qiqi Yan, Stefan Kusch, Melanie Klenke, Annette Gunkel, Lennart Wirthmueller, Marcel Wiermer
Summary: IMPORTIN-alpha 3/MOS6 is a key factor in regulating immune responses in Arabidopsis, primarily responsible for the nuclear transport of SNC1, playing an important role in autoimmunity and basal disease resistance.
Article
Virology
Liyan Cao, Fang Fu, Jianfei Chen, Hongyan Shi, Xin Zhang, Jianbo Liu, Da Shi, Yong Huang, Dewen Tong, Li Feng
Summary: Porcine parvovirus NS1 shuttles between the nucleus and cytoplasm via the CRM1-dependent nuclear export pathway and importin alpha/beta-mediated nuclear import pathway. The NESs and NLS of NS1 are essential for PPV replication. Blocking NS1's nuclear import or export inhibits PPV proliferation.
JOURNAL OF VIROLOGY
(2022)
Article
Multidisciplinary Sciences
Yong Ren, Meiling Chen, Guangxian Wu, Dongmei Ji, Grace Guoying Zhou, Pei-Gen Ren, Wenmin Fu
Summary: In glioblastoma cell line A172, genetic depletion of Mx2 enhances productive replication of oHSV-1 by promoting nuclear translocation of viral DNA and down-regulating innate antiviral response, ultimately increasing virus yield. Additionally, Mx2 knockdown alters the mRNA accumulation of innate immune genes in A172 cells, particularly DHX36 and MyD88, which further affects virus yield and activation of antiviral signaling pathways.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Olga Faerch, Roland Worth, Ikechukwu Achilonu, Heini Dirr
Summary: Chloride intracellular channel proteins (CLICs) are expressed widely and exhibit specific subcellular localization. CLIC1, CLIC3, and CLIC4 can be found within the nucleus, and the nuclear entry of CLIC4 is mediated through its specific nuclear localization sequence (NLS) interacting with the nuclear import mediator Imp alpha isoform 1. The interaction between CLIC NLSs and Imp alpha isoform 1 was weak, suggesting potential involvement of other factors or isoforms.
JOURNAL OF MOLECULAR RECOGNITION
(2023)
Article
Biochemistry & Molecular Biology
Shadma Fatima, Kylie M. Wagstaff, Sue Mei Lim, Jose M. Polo, Julia C. Young, David A. Jans
Summary: The nuclear transporter Importin 13 plays a critical role in maintaining pluripotency and differentiation of embryonic stem cells, with its loss leading to decreased proliferation, pluripotency transcript loss, and reduced mesodermal markers expression. The findings suggest that Imp13 is essential for ESC survival and early post-gastrulation differentiation.
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
(2021)
Article
Virology
Tetsuro Komatsu, Charlotte Quentin-Froignant, Irene Carlon-Andres, Floriane Lagadec, Fabienne Rayne, Jessica Ragues, Ralph H. Kehlenbach, Wenli Zhang, Anja Ehrhardt, Kerstin Bystricky, Renaud Morin, Jean-Michel Lagarde, Franck Gallardo, Harald Wodrich
JOURNAL OF VIROLOGY
(2018)
Article
Biochemical Research Methods
Imke Baade, Christiane Spillner, Kerstin Schmitt, Oliver Valerius, Ralph H. Kehlenbach
MOLECULAR & CELLULAR PROTEOMICS
(2018)
Article
Biochemistry & Molecular Biology
Marina Blenski, Ralph H. Kehlenbach
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2019)
Review
Cell Biology
Imke Baade, Ralph H. Kehlenbach
CURRENT OPINION IN CELL BIOLOGY
(2019)
Article
Biochemistry & Molecular Biology
Bastian Kindermann, Christina Valkova, Andreas Kraemer, Birgit Perner, Christian Engelmann, Laura Behrendt, Daniel Kritsch, Berit Jungnickel, Ralph H. Kehlenbach, Franz Oswald, Christoph Englert, Christoph Kaether
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Article
Biochemistry & Molecular Biology
Christina James, Marret Mueller, Martin W. Goldberg, Christof Lenz, Henning Urlaub, Ralph H. Kehlenbach
JOURNAL OF BIOLOGICAL CHEMISTRY
(2019)
Review
Biochemistry & Molecular Biology
Asaf Ashkenazy-Titelman, Yaron Shav-Tal, Ralph H. Kehlenbach
BIOCHEMICAL JOURNAL
(2020)
Article
Cell Biology
Marret Mueller, Christina James, Christof Lenz, Henning Urlaub, Ralph H. Kehlenbach
Article
Virology
Irene Carlon-Andres, Floriane Lagadec, Noemie Pied, Fabienne Rayne, Marie-Edith Lafon, Ralph H. Kehlenbach, Harald Wodrich
JOURNAL OF VIROLOGY
(2020)
Article
Multidisciplinary Sciences
Catherine P. Lavau, Waitman K. Aumann, Sei-Gyung K. Sze, Veerain Gupta, Katelyn Ripple, Sarah A. Port, Ralph H. Kehlenbach, Daniel S. Wechsler
Article
Cell Biology
Mohamed Hamed, Birgit Caspar, Sarah A. Port, Ralph H. Kehlenbach
Summary: Nup214 is a major nucleoporin involved in nuclear protein and mRNA export processes, interacting with the export receptor CRM1 via specific FG repeats and a classic NES. Mutations in the NES of Nup214 lead to nuclear accumulation, suggesting a role in NPC biogenesis and CRM1-dependent protein export terminal steps. The rescue of mutant Nup214 nuclear export with artificial NES indicates a potential mechanism for correct localization of Nup88.
JOURNAL OF CELL SCIENCE
(2021)
Review
Cell Biology
Christina James, Ralph H. Kehlenbach
Summary: Membrane contact sites play important roles in lipid transport, calcium homeostasis and other biological processes through tether proteins like VAPs, which interact with various organelles via different FFAT motifs. Recent studies have highlighted the complexity of interactions mediated by VAPs and their diverse interaction repertoire.
Article
Biochemistry & Molecular Biology
Christina James, Christof Lenz, Henning Urlaub, Ralph H. Kehlenbach
Summary: VAPB is a tail-anchored membrane protein of the endoplasmic reticulum that is also found at the inner nuclear membrane, involved in multiple protein interactions. A mutant version, P56S-VAPB, is linked to a familial form of amyotrophic lateral sclerosis, disrupting interactions with many known binding partners. Sequestosome 1 (SQSTM1) was identified as a major interaction partner of P56S-VAPB.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Virology
Floriane Lagadec, Irene Carlon-Andres, Jessica Ragues, Sarah Port, Harald Wodrich, Ralph H. Kehlenbach
Summary: After receptor-mediated endocytosis, adenoviral capsids travel to the nuclear envelope via microtubule organizing centers. Capsid disassembly and viral genome import into nuclei involve nuclear pore complexes and the nucleoporins Nup214 and Nup358. The nuclear export receptor CRM1 is required for this process and can promote capsid disassembly even in mitotic cells, indicating an export-independent role. Additionally, inhibition of CRM1 by leptomycin B leads to a blockage of capsid movement, and a mutant CRM1 variant, W142A P143A, shows deficiency in capsid disassembly but is still capable of nuclear export of cargo proteins.
JOURNAL OF VIROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Imke Baade, Saskia Hutten, Erin L. Sternburg, Marius Poerschke, Mario Hofweber, Dorothee Dormann, Ralph H. Kehlenbach
Summary: Fused in sarcoma (FUS) is a predominantly nuclear RNA-binding protein, with nuclear import receptors such as Transportin-1 and Transportin-2 facilitating its nuclear import by binding to the C-terminal nuclear localization signal of FUS. These receptors also suppress abnormal phase transitions of FUS in the cytoplasm, suggesting a network of importins may be utilized by aggregation-prone RNA-binding proteins for chaperoning and import functions.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)