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Table of Contents

November 2022 | Volume 5, No. 11

Research Articles

  • Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension
    Open Access
    Loss of Amphiregulin drives inflammation and endothelial apoptosis in pulmonary hypertension

    Jonathan Florentin, Jingsi Zhao, Yi-Yin Tai, Wei Sun, Lee L Ohayon, Scott P O’Neil, Anagha Arunkumar, Xinyi Zhang, Jianhui Zhu, Yassmin Al Aaraj, Annie Watson, John Sembrat, Mauricio Rojas, Stephen Y Chan, Partha Dutta

    Jonathan Florentin ... Partha Dutta

    Published 22 June 2022

    The key pathogenic features of pulmonary hypertension are endothelial apoptosis and vascular inflammation, which are caused by the down-regulation of Amphiregulin, accompanied by HIF-1a and BAD-mediated up-regulation of the target genes such as RRP1B, PHB2, and NCOA6.

  • Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome
    Open Access
    Activity-based probe profiling of RNF12 E3 ubiquitin ligase function in Tonne-Kalscheuer syndrome

    Francisco Bustos, Sunil Mathur, Carmen Espejo-Serrano, Rachel Toth, C James Hastie, Satpal Virdee, Greg M Findlay

    Francisco Bustos ... Greg M Findlay

    Published 28 June 2022

    The authors use photocrosslinking activity-based probes to monitor RNF12/RLIM E3 ubiquitin ligase activity and report the impact of Tonne-Kalscheuer syndrome (TOKAS) patient variants on catalysis.

  • Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants
    Open Access
    Multi-omics profiling identifies a deregulated FUS-MAP1B axis in ALS/FTD–associated UBQLN2 mutants

    Laura Strohm, Zehan Hu, Yongwon Suk, Alina Rühmkorf, Erin Sternburg, Vanessa Gattringer, Henrick Riemenschneider, Riccardo Berutti, Elisabeth Graf, Jochen H Weishaupt, Monika S Brill, Angelika B Harbauer, Dorothee Dormann, Jörn Dengjel, Dieter Edbauer, Christian Behrends

    Laura Strohm ... Christian Behrends

    Published 1 July 2022

    Analysis of ALS patient-derived and engineered cells revealed that mutant UBQLN2 increases mRNA and protein of MAP1B which is mediated by dephosphorylation of FUS within its RNA-binding domain.

  • Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models
    Open Access
    Heparan sulfate proteoglycans mediate prion-like α-synuclein toxicity in Parkinson’s in vivo models

    Merry Chen, Julie Vincent, Alexis Ezeanii, Saurabh Wakade, Shobha Yerigenahally, Danielle E Mor

    Merry Chen ... Danielle E Mor

    Published 5 July 2022

    This study offers new Caenorhabditis elegans models in which feeding with α-synuclein pre-formed fibrils results in prion-like aggregation of host α-synuclein and dopamine neuron degeneration, and these disease phenotypes are regulated by the heparan sulfate proteoglycan pathway.

  • Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome
    Open Access
    Proteins implicated in muscular dystrophy and cancer are functional constituents of the centrosome

    Lilli Winter, Monika Kustermann, Büsra Ernhofer, Harald Höger, Reginald E Bittner, Wolfgang M Schmidt

    Lilli Winter ... Wolfgang M Schmidt

    Published 5 July 2022

    This study demonstrates that the muscular dystrophy-associated proteins dystrophin, utrophin, dysferlin, and calpain-3 localize to the centrosome and that their absence leads to excess centrosomes, compromised nuclear morphology, impaired centrosome orientation, and defective microtubule nucleation.

  • CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7
    Open Access
    CryoEM of endogenous mammalian V-ATPase interacting with the TLDc protein mEAK-7

    Yong Zi Tan, Yazan M Abbas, Jing Ze Wu, Di Wu, Kristine A Keon, Geoffrey G Hesketh, Stephanie A Bueler, Anne-Claude Gingras, Carol V Robinson, Sergio Grinstein, John L Rubinstein

    Yong Zi Tan ... John L Rubinstein

    Published 6 July 2022

    The structure of mammalian V-ATPase with mEAK-7 shows how a TLDc domain-containing protein can bind the proton pump to form an activity-sensitive interaction.

  • Identification and characterization of a membrane receptor that binds to human STC1
    Open Access
    Identification and characterization of a membrane receptor that binds to human STC1

    Hin Ting Wan, Alice HM Ng, Wang Ka Lee, Feng Shi, Chris Kong-Chu Wong

    Hin Ting Wan ... Chris Kong-Chu Wong

    Published 7 July 2022

    A study using TriCEPS-based ligand–receptor methodology and surface plasmon resonance assays identified that human stanniocalcin-1 binds to insulin-like growth factor-2 receptors in human leukemia monocytic cells with high affinity.

  • KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells
    Open Access
    KIF24 depletion induces clustering of supernumerary centrosomes in PDAC cells

    Yu Mashima, Hayato Nohira, Hiroki Sugihara, Brian David Dynlacht, Tetsuo Kobayashi, Hiroshi Itoh

    Yu Mashima ... Hiroshi Itoh

    Published 8 July 2022

    Depletion of the centrosomal kinesin KIF24, known to restrain the assembly of primary cilia, suppresses multipolar spindle formation by clustering centrosomes in centrosome-amplified PDAC cells.

  • STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer
    Open Access
    STAT3 in tumor fibroblasts promotes an immunosuppressive microenvironment in pancreatic cancer

    Julia E Lefler, Catherine B MarElia-Bennett, Katie A Thies, Blake E Hildreth, Sudarshana M Sharma, Jason R Pitarresi, Lu Han, Caroline Everett, Christopher Koivisto, Maria C Cuitino, Cynthia D Timmers, Elizabeth O’Quinn, Melodie Parrish, Martin J Romeo, Amanda J Linke, G Aaron Hobbs, Gustavo Leone, Denis C Guttridge, Teresa A Zimmers, Gregory B Lesinski, Michael C Ostrowski

    Julia E Lefler ... Michael C Ostrowski

    Published 8 July 2022

    Using a dual recombinase mouse model of pancreatic cancer, investigators uncover genetic evidence for the role of STAT3 signaling in cancer-associated fibroblasts in promoting tumor progression and an immunosuppressive microenvironment.

  • PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance
    Open Access
    PVT1 is a stress-responsive lncRNA that drives ovarian cancer metastasis and chemoresistance

    Kevin Tabury, Mehri Monavarian, Eduardo Listik, Abigail K Shelton, Alex Seok Choi, Roel Quintens, Rebecca C Arend, Nadine Hempel, C Ryan Miller, Balázs Györrfy, Karthikeyan Mythreye

    Kevin Tabury ... Karthikeyan Mythreye

    Published 12 July 2022

    PVT1 is a YAP1 dependent stress responsive lncRNA that promotes ovarian cancer metastasis and chemoresistance, making PVT1 a promising therapeutic target.

  • Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in mice
    Open Access
    Lack of bombesin receptor–activated protein attenuates bleomycin-induced pulmonary fibrosis in mice

    Hui Wang, Wenrui Zhang, Rujiao Liu, Jiaoyun Zheng, Xueping Yao, Hui Chen, Jie Wang, Horst Christian Weber, Xiaoqun Qin, Yang Xiang, Chi Liu, Huijun Liu, Lang Pan, Xiangping Qu

    Hui Wang ... Xiangping Qu

    Published 12 July 2022

    Enhanced autophagic activity in fibroblasts due to lack of BRAP homologous protein might contribute to the resistance to pulmonary fibrosis in mice.

  • The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program
    Open Access
    The MLL3/4 complexes and MiDAC co-regulate H4K20ac to control a specific gene expression program

    Xiaokang Wang, Wojciech Rosikiewicz, Yurii Sedkov, Baisakhi Mondal, Tanner Martinez, Satish Kallappagoudar, Andrey Tvardovskiy, Richa Bajpai, Beisi Xu, Shondra M Pruett-Miller, Robert Schneider, Hans-Martin Herz

    Xiaokang Wang ... Hans-Martin Herz

    Published 12 July 2022

    The MLL3/4 histone methyltransferase complexes and the histone deacetylase complex MiDAC regulate the histone mark H4K20ac to calibrate gene expression of a common set of target genes.

  • ScRNA-seq expression of <em>IFI27</em> and <em>APOC2</em> identifies four alveolar macrophage superclusters in healthy BALF
    Open Access
    ScRNA-seq expression of IFI27 and APOC2 identifies four alveolar macrophage superclusters in healthy BALF

    Xin Li, Fred W Kolling, Daniel Aridgides, Diane Mellinger, Alix Ashare, Claudia V Jakubzick

    Xin Li ... Claudia V Jakubzick

    Published 12 July 2022

    There are at least 14 AM subtypes; their frequency, along with other immune cells, is highly conserved across individuals, suggesting a specific niche exists for each leukocyte population.

  • ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1
    Open Access
    ERK2 MAP kinase regulates SUFU binding by multisite phosphorylation of GLI1

    A Jane Bardwell, Beibei Wu, Kavita Y Sarin, Marian L Waterman, Scott X Atwood, Lee Bardwell

    A Jane Bardwell ... Lee Bardwell

    Published 13 July 2022

    As a mechanism of crosstalk, potentially relevant to cancer and developmental signaling, ERK2 MAP kinase phosphorylates the Hedgehog-pathway transcription factor GLI1 on three sites, promoting release of the negative regulator SUFU and the consequent activation of GLI1.

  • Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ<sub>42</sub> toxicity
    Open Access
    Decreasing pdzd8-mediated mito–ER contacts improves organismal fitness and mitigates Aβ42 toxicity

    Victoria L Hewitt, Leonor Miller-Fleming, Madeleine J Twyning, Simonetta Andreazza, Francesca Mattedi, Julien Prudent, Franck Polleux, Alessio Vagnoni, Alexander J Whitworth

    Victoria L Hewitt ... Alexander J Whitworth

    Published 13 July 2022

    The authors provide the first description of the impact of reducing pdzd8-mediated mito–ER contacts which prolongs lifespan, reduces age-related locomotor decline, and protects against mitochondrial toxins. pdzd8 loss is also protective against neuronal toxicity from Aβ42.

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Volume 5, No. 11
November 2022
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