Altered proteome in translation initiation fidelity defective eIF5 G31R mutant causes oxidative stress and DNA damage.

Autor: Ram AK; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, P.O Jatni, Khurda, 752050, India.; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, 400094, India., Mallik M; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, P.O Jatni, Khurda, 752050, India.; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, 400094, India., Reddy RR; Clinical Proteomics, DBT-Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Suryawanshi AR; Clinical Proteomics, DBT-Institute of Life Sciences, Bhubaneswar, Odisha, 751023, India., Alone PV; School of Biological Sciences, National Institute of Science Education and Research Bhubaneswar, P.O Jatni, Khurda, 752050, India. pankaj@niser.ac.in.; Homi Bhabha National Institute (HBNI), Anushakti Nagar, Mumbai, 400094, India. pankaj@niser.ac.in.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Mar 23; Vol. 12 (1), pp. 5033. Date of Electronic Publication: 2022 Mar 23.
DOI: 10.1038/s41598-022-08857-y
Abstrakt: The recognition of the AUG start codon and selection of an open reading frame (ORF) is fundamental to protein biosynthesis. Defect in the fidelity of start codon selection adversely affect proteome and have a pleiotropic effect on cellular function. Using proteomic techniques, we identified differential protein abundance in the translation initiation fidelity defective eIF5 G31R mutant that initiates translation using UUG codon in addition to the AUG start codon. Consistently, the eIF5 G31R mutant altered proteome involved in protein catabolism, nucleotide biosynthesis, lipid biosynthesis, carbohydrate metabolism, oxidation-reduction pathway, autophagy and re-programs the cellular pathways. The utilization of the upstream UUG codons by the eIF5 G31R mutation caused downregulation of uridylate kinase expression, sensitivity to hydroxyurea, and DNA damage. The eIF5 G31R mutant cells showed lower glutathione levels, high ROS activity, and sensitivity to H 2 O 2 .
(© 2022. The Author(s).)
Databáze: MEDLINE
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