IGFBP6 Modulates Proteostasis by Activating ATF4 Targets and Reducing ER Retrotranslocon Expression.

Autor: Kolodeeva OE; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia., Kolodeeva OE; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia., Antipenko ID; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia., Fatkulin AA; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia., Yakhina MR; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia., Makarova JA; Faculty of Biology and Biotechnology, National Research University Higher School of Economics, Moscow, Russia. jmakarova@hse.ru.
Jazyk: angličtina
Zdroj: Doklady. Biochemistry and biophysics [Dokl Biochem Biophys] 2024 Oct 31. Date of Electronic Publication: 2024 Oct 31.
DOI: 10.1134/S1607672924600714
Abstrakt: Reduced expression of the IGFBP6 protein leads to an increase in the metastatic potential of breast cancer (BC) cells. The level of protein synthesis in tumor cells is increased, leading to a compensatory adjustment of proteostasis. One of the tools used to study proteostasis is protein toxins of the RIP-II family, which irreversibly inactivate ribosomes (particularly, viscumin). We investigated the effect of IGFBP6 gene knockdown on the proteostasis in the BC cell line MDA-MB-231. Ribosomes from MDA-MB-231 IGFBP6 cells, knockdown for the IGFBP6 gene, are less efficiently modified by the toxin. This is probably due to the reduced transport of the viscumin catalytic subunit from the ER to the cytoplasm. MDA-MB-231 IGFBP6 cells showed reduced expression of the retrotranslocon HRD1/Derlin subunit, which is a component of the ER-associated protein degradation system (ERAD). For ATF4 transcription factor, which is a part of the ER unfolded protein response (UPR) pathway, an increased expression of its targets was found.
(© 2024. The Author(s).)
Databáze: MEDLINE
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