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Molecular Biology

  • MAP4K3 inhibits Sirtuin-1 to repress the LKB1–AMPK pathway to promote amino acid-dependent activation of the mTORC1 complex
    Open Access
    MAP4K3 inhibits Sirtuin-1 to repress the LKB1–AMPK pathway to promote amino acid-dependent activation of the mTORC1 complex

    Mary Rose Branch, Cynthia L Hsu, Kohta Ohnishi, Wen-Chuan Shen, Elian Lee, Jill Meisenhelder, Brett Winborn, Bryce L Sopher, J Paul Taylor, Tony Hunter, Albert R La Spada

    Mary Rose Branch ... Albert R La Spada

    Published 23 May 2023

    Our results reveal the existence of a novel signaling pathway linking amino acid satiety with MAP4K3-dependent suppression of SIRT1 to inactivate the repressive LKB1–AMPK pathway and thereby potently activate the mTORC1 complex to dictate the metabolic disposition of the cell.

  • The CHARGE syndrome-associated protein FAM172A controls AGO2 nuclear import
    Open Access
    The CHARGE syndrome-associated protein FAM172A controls AGO2 nuclear import

    Sephora Sallis, Félix-Antoine Bérubé-Simard, Benoit Grondin, Elizabeth Leduc, Fatiha Azouz, Catherine Bélanger, Nicolas Pilon

    Sephora Sallis ... Nicolas Pilon

    Published 23 May 2023

    AGO2 has long been known to shuttle between the cytosol and the nucleus of mammalian cells and this study helps to understand how this occurs.

  • Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum
    Open Access
    Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum

    Michele R Plewes, Emilia Przygrodzka, Corrine F Monaco, Alexandria P Snider, Jessica A Keane, Patrick D Burns, Jennifer R Wood, Andrea S Cupp, John S Davis

    Michele R Plewes ... John S Davis

    Published 15 May 2023

    This study investigates the early effects of PGF2α signaling on mitochondrial dynamics and mitophagy in bovine corpora lutea. Luteolytic mediator PGF2α, via PKC/ERK and AMPK signaling, activates mitochondrial fission and promotes PINK–Parkin mitophagy, placing mitochondria as novel targets in response to PGF2α.

  • Predictive data-driven modeling of C-terminal tyrosine function in the EGFR signaling network
    Open Access
    Predictive data-driven modeling of C-terminal tyrosine function in the EGFR signaling network

    Jacqueline S Gerritsen, Joseph S Faraguna, Rudy Bonavia, Frank B Furnari, Forest M White

    Jacqueline S Gerritsen ... Forest M White

    Published 11 May 2023

    The site-specific function of EGFR’s C-terminal tyrosines is interrogated by phosphotyrosine phosphoproteomics to build a data-driven model that links cell response to signaling nodes and elucidates novel associations in the EGFR signaling network.

  • Structural insights into ubiquitin chain cleavage by <em>Legionella</em> ovarian tumor deubiquitinases
    Open Access
    Structural insights into ubiquitin chain cleavage by Legionella ovarian tumor deubiquitinases

    Sangwoo Kang, Gyuhee Kim, Minhyeong Choi, Minwoo Jeong, Gerbrand J van der Heden van Noort, Soung-Hun Roh, Donghyuk Shin

    Sangwoo Kang ... Donghyuk Shin

    Published 26 April 2023

    Legionella possesses OTU deubiquitinases (Lot DUBs), which hinder the host ubiquitin system. We performed structural and biochemical analyses on the Lot DUBs and explained how Lot DUBs are different from other OTU-DUBs.

  • The cytochrome <em>b</em> carboxyl terminal region is necessary for mitochondrial complex III assembly
    Open Access
    The cytochrome b carboxyl terminal region is necessary for mitochondrial complex III assembly

    Daniel Flores-Mireles, Yolanda Camacho-Villasana, Madhurya Lutikurti, Aldo E García-Guerrero, Guadalupe Lozano-Rosas, Victoria Chagoya, Emma Berta Gutiérrez-Cirlos, Ulrich Brandt, Alfredo Cabrera-Orefice, Xochitl Pérez-Martínez

    Daniel Flores-Mireles ... Xochitl Pérez-Martínez

    Published 24 April 2023

    Synthesis/assembly of Cytb, encoded in the mitochondrial DNA, are regulated by the Cytb C-terminus. It modifies the interaction Cytb-Cbp3/Cbp6 to control Cytb and respiratory complex III biogenesis.

  • New botulinum neurotoxin constructs for treatment of chronic pain
    Open Access
    New botulinum neurotoxin constructs for treatment of chronic pain

    Charlotte Leese, Claire Christmas, Judit Mészáros, Stephanie Ward, Maria Maiaru, Stephen P Hunt, Bazbek Davletov

    Charlotte Leese ... Bazbek Davletov

    Published 11 April 2023

    A new technique to make therapeutic botulinum neurotoxins via isopeptide bonding is described. The novel elongated botulinum neurotoxin can treat nerve injury pain without causing muscle paralysis.

  • <em>arfA</em> antisense RNA regulates MscL excretory activity
    Open Access
    arfA antisense RNA regulates MscL excretory activity

    Rosa Morra, Fenryco Pratama, Thomas Butterfield, Geizecler Tomazetto, Kate Young, Ruth Lopez, Neil Dixon

    Rosa Morra ... Neil Dixon

    Published 3 April 2023

    Bacteria coordinate how they respond to translation and osmotic stress by using antisense RNA crosstalk between the genes involved in the respective stress response pathways.

  • The role of <em>Limch1</em> alternative splicing in skeletal muscle function
    Open Access
    The role of Limch1 alternative splicing in skeletal muscle function

    Matthew S Penna, Rong-Chi Hu, George G Rodney, Thomas A Cooper

    Matthew S Penna ... Thomas A Cooper

    Published 28 March 2023

    This works identifies a novel, alternatively spliced isoform of LIMCH1, that is, developmentally regulated and specific to skeletal muscle. Knocking out the six skeletal muscle–specific exons of LIMCH1 leads to impaired skeletal muscle function in vivo and ex vivo.

  • Interaction hub critical for telomerase recruitment and primer-template handling for catalysis
    Open Access
    Interaction hub critical for telomerase recruitment and primer-template handling for catalysis

    Shilpa Padmanaban, Valerie M Tesmer, Jayakrishnan Nandakumar

    Shilpa Padmanaban ... Jayakrishnan Nandakumar

    Published 24 March 2023

    By deleting, mutating, and adding back parts of the telomerase enzyme that extends chromosome ends, we uncover features important for its proper functioning in the cell.

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