The article with the participation of trainee researchers of the laboratory was accepted for publication in the journal ‘Reports of the Academy of Sciences. Life Sciences’

The publication is devoted to the study of proteostasis regulation

The level of protein synthesis is increased in tumour cells, which leads to compensatory readjustment of proteostasis. One of the tools for studying proteostasis is protein toxins of the RIP-II family that irreversibly inactivate ribosomes, in particular, viscumin. 

In this study, we investigated the effect of IGFBP6 gene knockdown on proteostasis of the breast cancer cell line MDA-MB-231. IGFBP6 protein regulates the rate of cell division and growth by altering the activity of growth factors. Reduced expression of IGFBP6 leads to increased metastatic potential of breast cancer cells.

IGFBP6 knockdown MDA-MB-231IGFBP6 ribosomes of IGFBP6 knockdown MDA-MB-231IGFBP6 cells were found to be less efficiently modified by the toxin.This appears to be due to reduced transport of the catalytic subunit viscumin from the endoplasmic reticulum (EPR) into the cytoplasm. 

In MDA-MB-231IGFBP6 cells, the expression of HRD1/Derlin retrotransposon subunits, a member of the EPR-associated protein degradation (ERAD) system, was reduced, see Figure. In addition, an increase in target expression of the ATF4 transcription factor, which is a component of the EPR response pathway to unfolded proteins (UPR), was detected.

Research interns Olga and Oksana Kolodeeva participated in the preparation and writing of the article.