The overexpressed transcription factor RGPR-p117 suppresses the proliferation of normal rat kidney proximal tubular epithelial NRK-52E cells: Involvement of diverse signaling pathways

• Published in: Life sciences (1973) 2022-10, Vol.306, p.120795-120795, Article 120795
• Main Authors: Yamaguchi, Masayoshi, Ghanem, Neda Z., Hashimoto, Kazunori, Ramos, Joe W., Murata, Tomiyasu
• Format: Article
• Language: English
• Subjects: agonists; Calcium signaling; cell cycle; Cell death; cell growth; Cell proliferation; consensus sequence; epithelium; fetal bovine serum; genes; Kidney proximal tubular epithelial cells; kidneys; mitogen-activated protein kinase; NRK-52E cells; promoter regions; protein kinase C; rats; Regucalcin; RGPR-p117; transcription factors; Transcriptional factor
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2022.120795

RGPR-p117 was originally discovered as a novel transcription factor, which specifically binds to a nuclear factor I (NFI) consensus motif TTGGC(N)6CC in the promoter region of the regucalcin gene. RGPR-p117 is also called as Lztr2 and SEC16B. The role of RGPR-p117 in cell regulation is poorly understood. This study was undertaken to determine whether the overexpression of RGPR-p117 impacts the proliferation of normal rat kidney proximal tubular epithelial NRK-52E cells in vitro. The NRK-52E wild-type cells and RGPR-p117-overexpressing NRK-52E cells were cultured in DMEM containing fetal bovine serum. The overexpression of RGPR-p117 repressed colony formation and proliferation of NRK-52E cells. Interestingly, RGPR-p117 overexpression blocked cell proliferation promoted by culturing with Bay K 8644, a calcium-entry agonist, and phorbol 12-myristate 13-acetate, an activator of protein kinase C. The depressive effects of RGPR-p117 overexpression on cell proliferation were not occurred by culturing with various inhibitors of cell cycle and intracellular signaling processes. RGPR-p117 overexpression increased the translocation of RGPR-p117 into the nucleus of NRK-52E cells. Mechanistically, RGPR-p117 overexpression diminished the levels of Ras, PI3 kinase, Akt, mitogen-activated protein kinase, and mTOR, while it raised the levels of p53, Rb, p21, and regucalcin. Furthermore, RGPR-p117 overexpression protected cell death caused by apoptosis-inducing factors, suggesting that the suppressive effects of RGPR-p117 on cell growth are independent of cell death. The present study demonstrates that the overexpressed transcription factor RGPR-p117 suppresses cell proliferation via targeting diverse signaling processes, suggesting a role of RGPR-p117 in cell regulation. [Display omitted]