title: ZAP is a CRM1-dependent nucleocytoplasmic shuttling protein.
abstract: The zinc finger antiviral protein (ZAP) is a recently isolated host antiviral factor. It specifically inhibits the replication of Moloney murine leukemia virus (MMLV) and Sindbis virus (SIN) by preventing the accumulation of viral RNA in the cytoplasm. In this report, we demonstrate that ZAP is predominantly localized in the cytoplasm at steady state but shuttles between the nucleus and the cytoplasm in a CRM1-dependent manner. Two nuclear localization sequences (NLS) and one nuclear export sequence (NES) were identified. One NLS was mapped to amino acids 68-RARVCRRK-75 and the other mapped to a region including amino acids K405 and K406. The NES was mapped to amino acids 284-LEDVSVDV-291. These findings help to understand why ZAP specifically prevents the accumulation of viral RNA in the cytoplasm. These findings also suggest possible functions of ZAP in the nucleus.
authors.affiliation: Institute of Microbiology, Chinese Academy of Sciences, Beijing 100080, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Liu
authors.forename: Guifang
authors.initials: G
authors.lastname: Chen
authors.forename: Xin
authors.initials: X
authors.lastname: Ji
authors.forename: Guangxia
authors.initials: G
authors.lastname: Gao
mesh_terms: D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D028884:Karyopherins / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D019913:Nuclear Localization Signals; D012367:RNA, Viral / Q000378:metabolism; D016601:RNA-Binding Proteins; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016335:Zinc Fingers; D000097606:Exportin 1 Protein
chemical_list: D002352:Carrier Proteins; D028884:Karyopherins; D019913:Nuclear Localization Signals; D012367:RNA, Viral; D016601:RNA-Binding Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D011993:Recombinant Fusion Proteins; D000097606:Exportin 1 Protein; C465959:Zc3hav1 protein, rat