• Title/Summary/Keyword: RalBP1

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The Molecular Functions of RalBP1 in Lung Cancer

  • Lee, Seunghyung
    • Biomedical Science Letters
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    • v.20 no.2
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    • pp.49-55
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    • 2014
  • RalBP1 is an ATP-dependent non-ABC transporter, responsible for the major transport function in many cells including many cancer cell lines, causing efflux of glutathione-electrophile conjugates of both endogenous metabolites and environmental toxins. RalBP1 is expressed in most human tissues, and is over-expressed in non-small cell lung cancer cell lines and in many other tumor types. Blockade of RalBP1 by various approaches has been shown to increase sensitivity to radiation and chemotherapeutic drugs, leading to cell apoptosis. In xenograft tumor models in mice, RalBP1 blockade or depletion results in complete and sustained regression across many cancer cell types including lung cancer cells. In addition to its transport function, RalBP1 has many other cellular and physiological functions, based on its domain structure which includes a unique Ral-binding domain and a RhoGAP catalytic domain, as well as docking sites for multiple signaling proteins. Additionally, RalBP1 is also important for stromal cell function in tumors, as it was recently shown to be required for efficient endothelial cell function and angiogenesis in solid tumors. In this review, we discuss the cellular and physiological functions of RalBP1 in normal and lung cancer cells.

RalA-binding Protein 1 is an Important Regulator of Tumor Angiogenesis (Tumor angiogenesis에 있어서 RLIP76의 중요성)

  • Lee, Seunghyung
    • Journal of Life Science
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    • v.24 no.5
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    • pp.588-593
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    • 2014
  • Tumor angiogenesis is important in tumorigenesis and therapeutic interventions in cancer. To know inhibitor and effector of tumor angiogenesis in cancer, the specific gene of tumor and angiogenesis may develop the mechanisms of cancer suppression and therapy. Recently, we described the role of RalA-binding protein 1 (RLIP76) in tumor angiogenesis. Tumor vascular volumes were diminished, and vessels were fewer in number, shorter, and narrower in RLIP76 knockout mice than in wild-type mice. Moreover, angiogenesis in basement membrane matrix plugs was blunted in the knockout mice in the absence of tumor cells, with endothelial cells isolated from the lungs of these animals exhibiting defects in migration, proliferation, and cord formation in vitro. RLIP76 is expressed in most human tissues and is overexpressed in many tumor types. In addition, the protein regulates tumorigenesis and angiogenesis in vivo and in vitro. As the export of chemotherapy agents is a prominent cellular function of RLIP76, it is a major factor in mechanisms of drug resistance. Moreover, RLIP76 acts as a selective effector of the small GTPase, R-Ras, and regulates R-Ras signaling, leading to cell spreading and migration. Furthermore, in skin carcinogenesis, RLIP76 knockout mice are resistant, with tumors that form showing diminished angiogenesis. Thus, RLIP76 is required for efficient endothelial cell function and angiogenesis in solid tumors.

Phosphorylation of REPS1 at Ser709 by RSK attenuates the recycling of transferrin receptor

  • Kim, Seong Heon;Cho, Jin-hwa;Park, Bi-Oh;Park, Byoung Chul;Kim, Jeong-Hoon;Park, Sung Goo;Kim, Sunhong
    • BMB Reports
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    • v.54 no.5
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    • pp.272-277
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    • 2021
  • RalBP1 associated EPS domain containing 1 (REPS1) is conserved from Drosophila to humans and implicated in the endocytic system. However, an exact role of REPS1 remains largely unknown. Here, we demonstrated that mitogen activated protein kinase kinase (MEK)-p90 ribosomal S6 Kinase (RSK) signaling pathway directly phosphorylated REPS1 at Ser709 upon stimulation by epidermal growth factor (EGF) and amino acid. While REPS2 is known to be involved in the endocytosis of EGF receptor (EGFR), REPS1 knockout (KO) cells did not show any defect in the endocytosis of EGFR. However, in the REPS1 KO cells and the KO cells reconstituted with a non-phosphorylatable REPS1 (REPS1 S709A), the recycling of transferrin receptor (TfR) was attenuated compared to the cells reconstituted with wild type REPS1. Collectively, we suggested that the phosphorylation of REPS1 at S709 by RSK may have a role of the trafficking of TfR.