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ISSN 1672-9145                                                Acta Biochim Biophys Sin 2004, 36(12): 817–823                                                  CN 31-1940/Q


A Putative NES Mediates Cytoplasmic Localization of Apoptin in Normal Cells

Qing-Ming WANG*, Guo-Cai FAN, Ji-Zhong CHEN, Hui-Peng CHEN, and Fu-Chu HE*

 

Department of Genomics and Proteomics, Beijing Institute of Radiation Medicine, Beijing 100850, China

 

Abstract        Apoptin, a protein expressed by chicken anemia virus, is found predominantly in the cytoplasm in normal cells, whereas it localizes  in the nucleus in transformed and malignant cells. However, the mechanisms that regulate the different subcellular localization of Apoptin in normal and tumor cells have not been fully clarified. In this work, a putative nuclear export signal (NES) in Apoptin was predicted. It was testified that the putative NES (pNES) of Apoptin was not a functional NES, but actually acted as a cytoplasmic retention signal. Deletion of the pNES led to the nuclear accumulation of Apoptin in normal cells. In addition, when a strong nuclear localization signal was introduced into Apoptin, it exclusively translocated to the nucleus in normal cells. These observations indicated that the cytoplasmic localization of Apoptin in normal cells results from the balance between cytoplasmic retention and nuclear import. On the other hand, the pNES was also proved to be necessary for Apoptin multimerization. Mutants lacking the pNES did not form obviously visible globular aggregates in normal or tumor cells.

 

Key words        Apoptin; nuclear localization signal; cytoplasmic retention signal; nuclear export signal

 

 

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Received: September 14, 2004        Accepted: October 18, 2004

*Corresponding authors:

Qing-Ming WANG: Fax, 86-10-68214653; E-mail, [email protected]  

Fu-Chu HE: E-mail, [email protected]