title: A CRM1-dependent nuclear export signal controls nucleocytoplasmic translocation of HSCARG, which regulates NF-κB activity.
abstract: HSCARG is a newly identified nuclear factor-κB (NF-κB) inhibitor that plays important roles in cell growth. Our previous study found that HSCARG could shuttle between the nucleus and cytoplasm by sensing the change in cellular redox states. To further investigate the mechanism of HSCARG translocation and its effect on the regulation of NF-κB activity, we identified a previously uncharacterized nuclear export signal (NES) at residues 272-278 of HSCARG that is required for its cytoplasmic translocation. This leucine-rich NES was found to be mediated by chromosome region maintenance 1. More importantly, accumulation of HSCARG in the nucleus occurred following a mutation in the NES or oxidative stress, which attenuated the inhibition of NF-κB by HSCARG. These results indicate that nucleocytoplasmic translocation of HSCARG plays an important role in fine-tuning NF-κB signaling.
authors.affiliation: State Key Lab of Protein and Plant Gene Research, School of Life Sciences, Peking University, Beijing 100871, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Tingting
authors.initials: T
authors.lastname: Li
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Peng
authors.forename: Junhong
authors.initials: J
authors.lastname: Guan
authors.forename: Shenshen
authors.initials: S
authors.lastname: Lai
authors.forename: Xiaofeng
authors.initials: X
authors.lastname: Zheng
mesh_terms: D021581:Active Transport, Cell Nucleus; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism*; D004252:DNA Mutational Analysis; D015972:Gene Expression Regulation, Neoplastic; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism / Q000502:physiology*; D007930:Leucine / Q000378:metabolism; D008856:Microscopy, Fluorescence / Q000379:methods; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism*; D049790:Nuclear Export Signals; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D000097606:Exportin 1 Protein
chemical_list: D028884:Karyopherins; D007930:Leucine; D016328:NF-kappa B; D049790:Nuclear Export Signals; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D000097606:Exportin 1 Protein; C520476:NMRAL1 protein, human