RGD Reference Report - Identification of nuclear export signals in antizyme-1. - Rat Genome Database

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Identification of nuclear export signals in antizyme-1.

Authors: Murai, Noriyuki  Murakami, Yasuko  Matsufuji, Senya 
Citation: Murai N, etal., J Biol Chem. 2003 Nov 7;278(45):44791-8. doi: 10.1074/jbc.M308059200. Epub 2003 Aug 26.
RGD ID: 401851056
Pubmed: PMID:12941943   (View Abstract at PubMed)
DOI: DOI:10.1074/jbc.M308059200   (Journal Full-text)

Antizyme-1 (AZ1) is a protein that negatively regulates polyamine synthesis by inhibiting the key synthetic enzyme ornithine decarboxylase and targeting it for degradation by the 26 S proteasome. Recent work shows that antizyme protein translocates to the nucleus during mouse development (Gritli-Linde, A., Nilssom, J., Bohlooly, Y. M., Heby, O., and Linde, A. (2001) Dev. Dyn. 220, 259-275). However, the significance and mechanism of this phenomenon remain unclear. In this study, we expressed AZ1 fused with enhanced green fluorescent protein (EGFP) to study its localization in a living cell. We found that EGFP-AZ1 was predominantly localized in the cytoplasm and that treatment with leptomycin B, a specific inhibitor of chromosomal region maintenance 1 (CRM1) induced nuclear accumulation of EGFP-AZ1 in Chinese hamster ovary and NIH3T3 cells. Two independent nuclear export signal (NES) sequences, each containing essential hydrophobic residues, were identified in the 50 N-terminal amino acid residues and in the central part of AZ1. The activity of the second NES was inhibited by an N-terminal adjacent region and was only revealed in N-terminal truncated constructs. Both NESs were active when fused to an artificial nuclear protein SV40-NLS-EGFP-EGFP. The ability of AZ1 to shuttle between the nucleus and the cytoplasm suggests that it has a novel function in the nucleus.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
OAZ1Humanleptomycin B increases localizationISOOaz1 (Rattus norvegicus)Leptomycin B increases localization of Oaz1 protein in the nucleusRGD 
Oaz1Ratleptomycin B increases localizationEXP Leptomycin B increases localization of Oaz1 protein in the nucleusRGD 
Oaz1Mouseleptomycin B increases localizationISOOaz1 (Rattus norvegicus)Leptomycin B increases localization of Oaz1 protein in the nucleusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Oaz1Ratcellular response to leptomycin B  IDA  RGD 

Cellular Component
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Oaz1Ratcytoplasm  IDA  RGD 
Oaz1Ratnucleus  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Oaz1  (ornithine decarboxylase antizyme 1)

Genes (Mus musculus)
Oaz1  (ornithine decarboxylase antizyme 1)

Genes (Homo sapiens)
OAZ1  (ornithine decarboxylase antizyme 1)


Additional Information