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Molecular and Cellular Biology, December 2003, p. 8751-8761, Vol. 23, No. 23
0270-7306/03/$08.00+0     DOI: 10.1128/MCB.23.23.8751-8761.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

A Multifunctional Domain in Human CRM1 (Exportin 1) Mediates RanBP3 Binding and Multimerization of Human T-Cell Leukemia Virus Type 1 Rex Protein

Yoshiyuki Hakata,1 Masami Yamada,1,2 and Hisatoshi Shida1*

Institute for Genetic Medicine, Hokkaido University, Kita-ku, Sapporo 060-0815, Japan,1 European Molecular Biology Laboratory, D-69117 Heidelberg, Germany2

Received 7 April 2003/ Returned for modification 19 May 2003/ Accepted 29 August 2003

Human CRM1 (hCRM1) functions in the Rex-mediated mRNA export of human T-cell leukemia virus type 1 (HTLV-1) as an export receptor and as an inducing factor for Rex multimerization on its cognate RNA. Although there are only 24 amino acid differences between hCRM1 and rat CRM1 (rCRM1), rCRM1 can hardly support Rex activity, suggesting a role for rCRM1 as a determinant restricting the host range of HTLV-1. Here, we used a series of mutants, which were generated by interchanging residues of these CRM1s, to examine the relationship of hCRM1 functions. The functions for Rex multimerization and binding to nuclear export signals are mapped to different amino acid residues, and these are separable, suggesting that CRM1 not only functions as an export receptor but also participates in the formation of the RNA export complex through higher-ordered interaction with Rex. The region for the interaction with RanBP3, comprising four residues (amino acids [aa] 411, 414, 474, and 481), and the region for Rex multimerization, including two residues (aa 411 and 414), form an overlapped domain. Our results provide the molecular basis underlying the species-specific ability of HTLV-1 to propagate in human cells.


* Corresponding author. Mailing address: Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan. Phone and fax: 81-11-706-7543. E-mail: hshida{at}imm.hokudai.ac.jp.


Molecular and Cellular Biology, December 2003, p. 8751-8761, Vol. 23, No. 23
0022-538X/03/$08.00+0     DOI: 10.1128/MCB.23.23.8751-8761.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.




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