Ras-activated RSK1 phosphorylates EBP50 to regulate its nuclear localization and promote cell proliferation
Journal
Oncotarget
Journal Volume
7
Journal Issue
9
Pages
10283-10296
Date Issued
2016
Author(s)
Lim H.
Abstract
Differential subcellular localization of EBP50 leads to its controversial role in cancer biology either as a tumor suppressor when it resides at the membrane periphery, or a tumor facilitator at the nucleus. However, the mechanism behind nuclear localization of EBP50 remains unclear. A RNA interference screening identified the downstream effector of the Ras-ERK cascade, RSK1, as the molecule unique for nuclear transport of EBP50. RSK1 binds to EBP50 and phosphorylates it at a conserved threonine residue at position 156 (T156) under the regulation of growth factor. Mutagenesis experiments confirmed the significance of T156 residue in nuclear localization of EBP50, cellular proliferation, and oncogenic transformation. Our study sheds light on a possible therapeutic strategy targeting at this aberrant nuclear expression of EBP50 without affecting the normal physiological function of EBP50 at other subcellular localization.
SDGs
Other Subjects
EBP50 protein; growth factor; Ras protein; RSK1 protein; S6 kinase; scaffold protein; threonine; unclassified drug; phosphoprotein; protein binding; RPS6KA1 protein, human; S6 kinase; small interfering RNA; sodium proton exchange protein; sodium-hydrogen exchanger regulatory factor; animal cell; animal experiment; animal model; animal tissue; Article; carcinogenesis; cell nucleus; cell proliferation; cellular distribution; controlled study; HEK293 cell line; HeLa cell line; human; human cell; MDCK cell line; mitosis; mouse; mutagenesis; nonhuman; PDZ domain; protein phosphorylation; protein protein interaction; RNA interference; signal transduction; tumor xenograft; animal; binding site; cell nucleus; cell proliferation; genetics; metabolism; nonobese diabetic mouse; nucleocytoplasmic transport; phosphorylation; physiology; SCID mouse; tumor cell line; Active Transport, Cell Nucleus; Animals; Binding Sites; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; HEK293 Cells; HeLa Cells; Humans; Mice; Mice, Inbred NOD; Mice, SCID; Phosphoproteins; Phosphorylation; Protein Binding; Ribosomal Protein S6 Kinases, 90-kDa; RNA Interference; RNA, Small Interfering; Sodium-Hydrogen Antiporter
Publisher
Impact Journals LLC
Type
journal article