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J. Biol. Chem., Vol. 276, Issue 51, 48596-48607, December 21, 2001
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From the The Ret finger protein (RFP) was
identified initially as an oncogene product and belongs to a family of
proteins that contain a tripartite motif consisting of a RING finger, a
B box, and a coiled-coil domain. RFP represses transcription by
interacting with Enhancer of Polycomb and is localized to the cytoplasm
or nucleus depending on the cell type. Here, we have identified the nuclear export signal (NES) located in the coiled-coil region of RFP.
Mutation of this NES or treatment with leptomycin B abrogated the
nuclear export of RFP in NIH3T3 cells. In addition, fusion of this NES
to other nuclear proteins, such as yeast transcription factor Gal4,
resulted in their release into the cytoplasm of NIH3T3 cells. Although
the NES function of RFP in HepG2 cells is masked by another domain in
RFP or by another protein,
12-O-tetradecanoylphorbol-13-acetate treatment or
overexpression of constitutively active protein kinase C
Intracellular Localization of the Ret Finger Protein
Depends on a Functional Nuclear Export Signal and Protein Kinase C
Activation*
,§,§
Laboratory of Molecular Genetics, RIKEN
Tsukuba Institute, and § Core Research for Evolutionary
Science and Technology (CREST) Project of Japan Science and Technology
Corporation, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, and the
¶ Department of Molecular Biology, Yokohama City University School
of Medicine, 3-9 Fuku-ura, Kanazawa-ku, Yokohama 236, Japan
(PKC)
abrogated masking, leading to the cytoplasmic localization of RFP.
Furthermore, treatment of NIH3T3 cells with PKC inhibitors blocked the
function of NES, resulting in nuclear localization of RFP. Thus, the
nuclear export of RFP is regulated positively by PKC activation.
However, RFP was not a direct substrate of PKC, and additional
signaling pathways may be involved in the regulation of nuclear export
of RFP.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
To whom correspondence should be addressed: Laboratory of
Molecular Genetics, RIKEN Tsukuba Institute, 3-1-1 Koyadai, Tsukuba, Ibaraki 305-0074, Japan. Tel.: 81-298-36-9031; Fax:
81-298-36-9030; E-mail: sishii@rtc.riken.go.jp.
Copyright © 2001 by The American Society for Biochemistry and Molecular Biology, Inc.
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