Articles producció científica> Enginyeria Electrònica, Elèctrica i Automàtica

CD98hc (SLC3A2) sustains amino acid and nucleotide availability for cell cycle progression

  • Dades identificatives

    Identificador: imarina:5873548
    Autors:
    Cano-Crespo, SaraChillaron, JosepJunza, AlexandraFernandez-Miranda, GonzaloGarcia, JuditPolte, Christinede la Ballina, Laura RIgnatova, ZoyaYanes, OscarZorzano, AntonioStephan-Otto Attolini, CamillePalacin, Manuel
    Resum:
    CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.
  • Altres:

    Autor segons l'article: Cano-Crespo, Sara; Chillaron, Josep; Junza, Alexandra; Fernandez-Miranda, Gonzalo; Garcia, Judit; Polte, Christine; de la Ballina, Laura R; Ignatova, Zoya; Yanes, Oscar; Zorzano, Antonio; Stephan-Otto Attolini, Camille; Palacin, Manuel
    Departament: Enginyeria Electrònica, Elèctrica i Automàtica
    Autor/s de la URV: Junza Martínez, Alexandra / Yanes Torrado, Óscar
    Paraules clau: Therapeutic target Slc3a2 protein, human Replication stress Regulated eif2-alpha kinase Purine synthesis Oxidative stress Nutrient transporters Nucleotides Nasopharyngeal carcinoma Mechanistic target of rapamycin complex 1 Mammalian target Humans Glutamine-metabolism Gene knockout techniques Gene expression profiling Fusion regulatory protein 1, heavy chain Dna-damage response Dna repair Dna damage Cell division Cell cycle Amino acids, branched-chain Amino acids, aromatic Amino acids
    Resum: CD98 heavy chain (CD98hc) forms heteromeric amino acid (AA) transporters by interacting with different light chains. Cancer cells overexpress CD98hc-transporters in order to meet their increased nutritional and antioxidant demands, since they provide branched-chain AA (BCAA) and aromatic AA (AAA) availability while protecting cells from oxidative stress. Here we show that BCAA and AAA shortage phenocopies the inhibition of mTORC1 signalling, protein synthesis and cell proliferation caused by CD98hc ablation. Furthermore, our data indicate that CD98hc sustains glucose uptake and glycolysis, and, as a consequence, the pentose phosphate pathway (PPP). Thus, loss of CD98hc triggers a dramatic reduction in the nucleotide pool, which leads to replicative stress in these cells, as evidenced by the enhanced DNA Damage Response (DDR), S-phase delay and diminished rate of mitosis, all recovered by nucleoside supplementation. In addition, proper BCAA and AAA availability sustains the expression of the enzyme ribonucleotide reductase. In this regard, BCAA and AAA shortage results in decreased content of deoxynucleotides that triggers replicative stress, also recovered by nucleoside supplementation. On the basis of our findings, we conclude that CD98hc plays a central role in AA and glucose cellular nutrition, redox homeostasis and nucleotide availability, all key for cell proliferation.
    Àrees temàtiques: Zootecnia / recursos pesqueiros Saúde coletiva Química Psicología Odontología Nutrição Multidisciplinary sciences Multidisciplinary Medicina veterinaria Medicina iii Medicina ii Medicina i Materiais Matemática / probabilidade e estatística Letras / linguística Interdisciplinar Geografía Geociências Farmacia Engenharias iv Engenharias iii Engenharias ii Enfermagem Educação física Educação Economia Ciências biológicas iii Ciências biológicas ii Ciências biológicas i Ciências ambientais Ciências agrárias i Ciência de alimentos Ciência da computação Biotecnología Biodiversidade Astronomia / física
    Accès a la llicència d'ús: https://creativecommons.org/licenses/by/3.0/es/
    ISSN: 20452322
    Adreça de correu electrònic de l'autor: oscar.yanes@urv.cat alexandra.junza@urv.cat
    Identificador de l'autor: 0000-0003-3695-7157 0000-0001-7205-0419
    Data d'alta del registre: 2024-10-12
    Versió de l'article dipositat: info:eu-repo/semantics/publishedVersion
    Enllaç font original: https://www.nature.com/articles/s41598-019-50547-9
    URL Document de llicència: https://repositori.urv.cat/ca/proteccio-de-dades/
    Referència a l'article segons font original: Scientific Reports. 9 (1): 14065-14065
    Referència de l'ítem segons les normes APA: Cano-Crespo, Sara; Chillaron, Josep; Junza, Alexandra; Fernandez-Miranda, Gonzalo; Garcia, Judit; Polte, Christine; de la Ballina, Laura R; Ignatova, (2019). CD98hc (SLC3A2) sustains amino acid and nucleotide availability for cell cycle progression. Scientific Reports, 9(1), 14065-14065. DOI: 10.1038/s41598-019-50547-9
    DOI de l'article: 10.1038/s41598-019-50547-9
    Entitat: Universitat Rovira i Virgili
    Any de publicació de la revista: 2019
    Tipus de publicació: Journal Publications
  • Paraules clau:

    Multidisciplinary,Multidisciplinary Sciences
    Therapeutic target
    Slc3a2 protein, human
    Replication stress
    Regulated eif2-alpha kinase
    Purine synthesis
    Oxidative stress
    Nutrient transporters
    Nucleotides
    Nasopharyngeal carcinoma
    Mechanistic target of rapamycin complex 1
    Mammalian target
    Humans
    Glutamine-metabolism
    Gene knockout techniques
    Gene expression profiling
    Fusion regulatory protein 1, heavy chain
    Dna-damage response
    Dna repair
    Dna damage
    Cell division
    Cell cycle
    Amino acids, branched-chain
    Amino acids, aromatic
    Amino acids
    Zootecnia / recursos pesqueiros
    Saúde coletiva
    Química
    Psicología
    Odontología
    Nutrição
    Multidisciplinary sciences
    Multidisciplinary
    Medicina veterinaria
    Medicina iii
    Medicina ii
    Medicina i
    Materiais
    Matemática / probabilidade e estatística
    Letras / linguística
    Interdisciplinar
    Geografía
    Geociências
    Farmacia
    Engenharias iv
    Engenharias iii
    Engenharias ii
    Enfermagem
    Educação física
    Educação
    Economia
    Ciências biológicas iii
    Ciências biológicas ii
    Ciências biológicas i
    Ciências ambientais
    Ciências agrárias i
    Ciência de alimentos
    Ciência da computação
    Biotecnología
    Biodiversidade
    Astronomia / física
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