title: Ribosomal protein L19 overexpression activates the unfolded protein response and sensitizes MCF7 breast cancer cells to endoplasmic reticulum stress-induced cell death.
abstract: Although first identified for their roles in protein synthesis, certain ribosomal proteins exert pleiotropic physiological functions in the cell. Ribosomal protein L19 is overexpressed in breast cancer cells by amplification and copy number variation. In this study, we examined the novel pro-apoptotic role of ribosomal protein L19 in the breast cancer cell line MCF7. Overexpression of RPL19 sensitized MCF7 cells to endoplasmic reticulum stress-induced cell death. RPL19 overexpression itself was not cytotoxic; however, cell death induction was enhanced when RPL19 overexpressing cells were incubated with endoplasmic reticulum stress-inducing agents, and this sensitizing effect was specific to MCF7 cells. Examination of the cell signaling pathways that mediate the unfolded protein response (UPR) revealed that overexpression of RPL19 induced pre-activation of the UPR, including phosphorylation of pERK-like ER kinase (PERK), phosphorylation of eukaryotic translation initiation factor 2 alpha (eIF2α), and activation of p38 MAPK-associated stress signaling. Our findings suggest that upregulation of RPL19 induces ER stress, resulting in increased sensitivity to ER stress and enhanced cell death in MCF7 breast cancer cells.
authors.affiliation: ASAN Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea.
authors.forename: Mina
authors.initials: M
authors.lastname: Hong
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Wonkwang University, Iksan, Chonbuk, Republic of Korea. Electronic address: hrkimdp@wonkwang.ac.kr.
authors.forename: HyungRyong
authors.initials: H
authors.lastname: Kim
authors.affiliation: ASAN Institute for Life Sciences, ASAN Medical Center, Seoul, Republic of Korea; Department of Medicine, University of Ulsan College of Medicine, Seoul, Republic of Korea. Electronic address: ik.kim@amc.seoul.kr.
authors.forename: Inki
authors.initials: I
authors.lastname: Kim
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism*; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D018384:Oxidative Stress; D011489:Protein Denaturation; D017510:Protein Folding; D012269:Ribosomal Proteins / Q000737:chemistry / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: C489092:RPL19 protein, human; D012269:Ribosomal Proteins
keywords: Breast cancer; ER stress; Ribosomal protein L19; Unfolded protein response