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The C‐terminus of apoptin represents a unique tumor cell‐enhanced nuclear targeting module
Author(s) -
Kuusisto Henna V.,
Wagstaff Kylie M.,
Alvisi Gualtiero,
Jans David A.
Publication year - 2008
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.23884
Subject(s) - nuclear localization sequence , nls , context (archaeology) , nuclear transport , nuclear export signal , cell , biology , nuclear protein , cell nucleus , microbiology and biotechnology , cancer research , nucleus , biochemistry , gene , paleontology , transcription factor
Chicken anemia virus viral protein 3 (VP3 or apoptin) localizes more efficiently in the nucleus of transformed than nontransformed cells. Although previous studies implicate the C‐terminus of apoptin as being responsible, the molecular basis is controversial, and the extent to which altered nuclear transport efficiency in tumor cells may influence VP3 differential targeting unclear. Here we establish that the C‐terminus of VP3 (residues 74–121), out of the context of the full‐length protein, is indeed sufficient for tumor cell‐enhanced nuclear targeting through phosphoinhibition of VP3 (74–121)‐mediated nuclear export occurring exclusively in tumor cells. Importantly, we show that VP3 (74–121) is unique in showing tumor cell‐enhanced nuclear targeting in that other NLS‐containing proteins fail to show differential localization in human osteosarcoma cells compared to their normal isogenic counterparts. Thus, the C‐terminus of VP3 represents a unique tumor cell‐enhanced nuclear targeting module with potential application in tumor cell‐specific drug delivery. © 2008 Wiley‐Liss, Inc.