The kinase PERK represses translation of the G-protein-coupled receptor LGR5 and receptor tyrosine kinase ERBB3 during ER stress in cancer cells [Protein Synthesis and Degradation]

In this study, we show that a stem-cell marker protein, leucine-rich repeat-containing G-protein–coupled receptor 5 (LGR5), is rapidly depleted in colon cancer cells during ER stress, an effect that depended on the PERK-mediated translational repression. Indeed, the PERK inhibition led to the accumulation of premature, underglycosylated forms of LGR5, which were produced only at low levels during proper PERK activation. Unlike the mature LGR5 form, which is constitutively degraded regardless of PERK activation, the underglycosylated LGR5 exhibited a prolonged half-life and accumulated inside the cells without being expressed on the cell surface. We also found that Erb-B2 receptor tyrosine kinase 3 (ERBB3) is subjected to a similarly-regulated depletion by PERK, whereas the epidermal growth factor receptor (EGFR), stress-inducible heat-shock protein family A (Hsp70) member 5 (HSPA5), and anterior gradient 2 protein-disulfide isomerase family member (AGR2) were relatively. insensitive to the PERK-mediated repression of translation. These results indicate that LGR5 and ERBB3 are targets for PERK-mediated translational repression during ER stress

Source: Journal of Biological Chemistry - April 2, 2020 Category: Chemistry Authors: Yuka Okamoto, Takuya Saito, Yuri Tani, Tamami Toki, Akiko Hasebe, Masaru Koido, Akihiro Tomida Tags: Cell Biology Source Type: research