title: Emerin suppresses Notch signaling by restricting the Notch intracellular domain to the nuclear membrane.
abstract: Emerin is an inner nuclear membrane protein that is involved in maintaining the mechanical integrity of the nuclear membrane. Increasing evidence supports the involvement of emerin in the regulation of gene expression; however, its precise function remains to be elucidated. Here, we show that emerin downregulated genes downstream of Notch signaling, which are activated exclusively by the Notch intracellular domain (NICD). Deletion mutant experiments revealed that the transmembrane domain of emerin is important for the inhibition of Notch signaling. Emerin interacted directly and colocalized with the NICD at the nuclear membrane. Emerin knockdown induced the phosphorylation of ERK and AKT, increased endogenous Notch signaling, and inhibited hydrogen peroxide-induced apoptosis in HeLa cells. Notably, the downregulation of barrier-to-autointegration factor (BAF) or lamin A/C increased Notch signaling by inducing the release of emerin into the cytosol, implying that nuclear membrane-bound emerin acts as an endogenous inhibitor of Notch signaling. Taken together, our results indicate that emerin negatively regulates Notch signaling by promoting the retention of the NICD at the nuclear membrane. This mechanism could constitute a new therapeutic target for the treatment of emerin-related diseases.
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 05006, Republic of Korea.
authors.forename: Byongsun
authors.initials: B
authors.lastname: Lee
authors.affiliation: Laboratory for Cancer & Stem Cell Biology, Plant Engineering Institute, Sejong University, Seoul 05006, Republic of Korea.
authors.forename: Tae-Hee
authors.initials: TH
authors.lastname: Lee
authors.affiliation: Department of Molecular Biology, Sejong University, Seoul 05006, Republic of Korea; Laboratory for Cancer & Stem Cell Biology, Plant Engineering Institute, Sejong University, Seoul 05006, Republic of Korea. Electronic address: jkshim@sejong.ac.kr.
authors.forename: Jaekyung
authors.initials: J
authors.lastname: Shim
mesh_terms: D002470:Cell Survival; D005786:Gene Expression Regulation / Q000502:physiology; D055785:Gene Knockdown Techniques; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism / Q000502:physiology*; D009685:Nuclear Envelope / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding; D051880:Receptors, Notch / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D008565:Membrane Proteins; D009687:Nuclear Proteins; D051880:Receptors, Notch; C092710:emerin
keywords: Emerin; Notch signaling; Nuclear membrane