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