RESEARCH ARTICLE BIG3 Inhibits the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in Breast Cancer Cells Nam-Hee Kim1,2, Tetsuro Yoshimaru1, Yi-An Chen3, Taisuke Matsuo1¤, Masato Komatsu1, Yasuo Miyoshi4, Eiji Tanaka2, Mitsunori Sasa5, Kenji Mizuguchi3, Toyomasa Katagiri1* 1 Division of Genome Medicine, Institute for Genome Research, Tokushima University, Tokushima, Japan, 2 Department of Orthodontics and Dentofacial Orthopedics, Institute of Biomedical Sciences, Tokushima University Graduate School, Tokushima, Japan, 3 National Institute of Biomedical Innovation, Osaka, Japan, 4 Department of Surgery, Division of Breast and Endocrine Surgery, Hyogo College of Medicine, Hyogo, Japan, 5 Department of Surgery, Tokushima Breast Care Clinic, Tokushima, Japan ¤ Current address: Department of Advanced Pharmaceutics, School of Pharmacy, Iwate Medical University, Iwate, Japan *
[email protected] OPEN ACCESS Citation: Kim N-H, Yoshimaru T, Chen Y-A, Matsuo T, Komatsu M, Miyoshi Y, et al. (2015) BIG3 Inhibits Abstract the Estrogen-Dependent Nuclear Translocation of PHB2 via Multiple Karyopherin-Alpha Proteins in We recently reported that brefeldin A-inhibited guanine nucleotide-exchange protein 3 Breast Cancer Cells. PLoS ONE 10(6): e0127707. (BIG3) binds Prohibitin 2 (PHB2) in cytoplasm, thereby causing a loss of function of the doi:10.1371/journal.pone.0127707 PHB2 tumor suppressor in the nuclei of breast cancer cells. However, little is known regard- Academic Editor: Hong Wanjin, Institute of ing the mechanism by which BIG3 inhibits the nuclear translocation of PHB2 into breast Molecular and Cell Biology, Biopolis, UNITED cancer cells. Here, we report that BIG3 blocks the estrogen (E2)-dependent nuclear import STATES of PHB2 via the karyopherin alpha (KPNA) family in breast cancer cells.