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Chemical Biology

  • A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95
    Open Access
    A new ferrocene derivative blocks K-Ras localization and function by oxidative modification at His95

    Kristen M Rehl, Jayaraman Selvakumar, Rhonda L Pitsch, Don Hoang, Kuppuswamy Arumugam, Sean W Harshman, Alemayehu A Gorfe, Kwang-Jin Cho

    Kristen M Rehl ... Kwang-Jin Cho

    Published 4 September 2023

    We report redox system regulates KRAS localization and activity via oxidation at His95 residue, and proposes a role of oncogenic K-Ras in the antioxidant-induced growth and metastasis of KRAS-driven cancers.

  • A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance
    Open Access
    A novel antifolate suppresses growth of FPGS-deficient cells and overcomes methotrexate resistance

    Felix van der Krift, Dick W Zijlmans, Rhythm Shukla, Ali Javed, Panagiotis I Koukos, Laura LE Schwarz, Elpetra PM Timmermans-Sprang, Peter EM Maas, Digvijay Gahtory, Maurits van den Nieuwboer, Jan A Mol, Ger J Strous, Alexandre MJJ Bonvin, Mario van der Stelt, Edwin JA Veldhuizen, Markus Weingarth, Michiel Vermeulen, Judith Klumperman, Madelon M Maurice

    Felix van der Krift ... Madelon M Maurice

    Published 17 August 2023

    Mechanistic characterization of a novel, lipophilic antifolate that suppresses growth of FPGS-deficient cells that are linked to methotrexate resistance and relapse in cancer patients.

  • FAT10 and NUB1L cooperate to activate the 26S proteasome
    Open Access
    FAT10 and NUB1L cooperate to activate the 26S proteasome

    Florian Brockmann, Nicola Catone, Christine Wünsch, Fabian Offensperger, Martin Scheffner, Gunter Schmidtke, Annette Aichem

    Florian Brockmann ... Annette Aichem

    Published 15 May 2023

    26S proteasome activation is achieved by the collective binding of the ubiquitin-like modifier FAT10 and its interaction partner NUB1L, causing gate opening in a USP14-independent way.

  • Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2
    Open Access
    Membrane cholesterol regulates inhibition and substrate transport by the glycine transporter, GlyT2

    Zachary J Frangos, Katie A Wilson, Heather M Aitken, Ryan Cantwell Chater, Robert J Vandenberg, Megan L O’Mara

    Zachary J Frangos ... Megan L O’Mara

    Published 23 January 2023

    Cholesterol binds to the GlyT2 SLC6 transporter, enhancing the effect of bioactive lipid analgesics, providing new therapeutic avenues to treat neuropathic pain and target SLC6 transporters.

  • An unconventional cancer-promoting function of methamphetamine in hepatocellular carcinoma
    Open Access
    An unconventional cancer-promoting function of methamphetamine in hepatocellular carcinoma

    Zizhen Si, GuanJun Yang, Xidi Wang, Zhaoying Yu, Qian Pang, Shuangshuang Zhang, Liyin Qian, Yuer Ruan, Jing Huang, Liu Yu

    Zizhen Si ... Liu Yu

    Published 20 January 2023

    METH use is associated with a higher incidence of hepatocellular carcinoma (HCC) in METH abusers and rehabilitees. METH exposure promotes HCC progression by ROS-mediated activation of the Ras/MEK/ERK signaling pathway. Clearance of ROS by NAC abolishes METH-induced HCC progression.

  • The βI domain promotes active β1 integrin clustering into mature adhesion sites
    Open Access
    The βI domain promotes active β1 integrin clustering into mature adhesion sites

    Giulia Mana, Donatella Valdembri, Janet A Askari, Zhenhai Li, Patrick Caswell, Cheng Zhu, Martin J Humphries, Christoph Ballestrem, Guido Serini

    Giulia Mana ... Guido Serini

    Published 21 November 2022

    Mana et al show that the extracellular headpiece βI domain is involved in conformationally active β1 integrin clustering, fibrillar adhesion formation, incorporation of soluble fibronectin dimers into fibrillar polymers, and extracellular matrix–dependent endothelial cell migration.

  • SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members
    Open Access
    SMA-linked SMN mutants prevent phase separation properties and SMN interactions with FMRP family members

    Olivier Binda, Franceline Juillard, Julia Novion Ducassou, Constance Kleijwegt, Geneviève Paris, Andréanne Didillon, Faouzi Baklouti, Armelle Corpet, Yohann Couté, Jocelyn Côté, Patrick Lomonte

    Olivier Binda ... Patrick Lomonte

    Published 14 November 2022

    The survival motor neuron (SMN) protein associates with translation regulators and phase-separates into RNA-stabilized droplets that are likely candidates for the formation of nuclear and cytoplasmic membraneless organelles.

  • Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis
    Open Access
    Tanshinone functions as a coenzyme that confers gain of function of NQO1 to suppress ferroptosis

    Tian-Xiang Wang, Kun-Long Duan, Zi-Xuan Huang, Zi-An Xue, Jun-Yun Liang, Yongjun Dang, Ao Zhang, Yue Xiong, Chunyong Ding, Kun-Liang Guan, Hai-Xin Yuan

    Tian-Xiang Wang ... Hai-Xin Yuan

    Published 1 November 2022

    NQO1 catalyzes the reduction of tanshinones to detoxify lipid peroxyl radicals and inhibit ferroptosis both in vitro and in vivo, providing a molecular mechanism for the therapeutic effects of tanshinones, such as cardiac protection.

  • Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16
    Open Access
    Non-canonical miRNA-RNA base-pairing impedes tumor suppressor activity of miR-16

    Anaïs M Quéméner, Laura Bachelot, Marc Aubry, Stéphane Avner, Delphine Leclerc, Gilles Salbert, Florian Cabillic, Didier Decaudin, Bernard Mari, Frédéric Mouriaux, Marie-Dominique Galibert, David Gilot

    Anaïs M Quéméner ... David Gilot

    Published 6 October 2022

    In uveal melanoma tumors, the RNA decay activity of the tumor suppressor miR-16 is impaired by sponge RNAs. These RNAs defined a powerful signature to predict overall survival.

  • Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferase
    Open Access
    Insight into the mechanism of DNA synthesis by human terminal deoxynucleotidyltransferase

    Aleksandra A Kuznetsova, Timofey E Tyugashev, Irina V Alekseeva, Nadezhda A Timofeyeva, Olga S Fedorova, Nikita A Kuznetsov

    Aleksandra A Kuznetsova ... Nikita A Kuznetsov

    Published 1 August 2022

    The role of metal ions and specific interactions of dNTP with active-site amino acid residues in the mechanisms underlying the recognition of nucleoside triphosphates by human terminal deoxynucleotidyltransferase were revealed by pre–steady-state kinetics and molecular dynamics approaches.

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