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J. Biol. Chem., Vol. 277, Issue 12, 10315-10322, March 22, 2002
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From the Hepatoma-derived growth factor (HDGF) is the
original member of the HDGF family of proteins, which contains a
well-conserved N-terminal amino acid sequence (homologous
to the amino terminus of HDGF;
hath) and nuclear localization signals (NLSs) in gene-specific regions other than the hath region. In addition to a bipartite NLS in a
gene-specific region, an NLS-like sequence is also found in the hath
region. In cells expressing green fluorescence protein (GFP)-HDGF,
green fluorescence was observed in the nucleus, whereas it was detected
in the cytoplasm of cells expressing GFP-HDGF with both NLSs mutated or
deleted. GFP-hath protein (GFP-HATH) was distributed mainly in the
nucleus, although some was present in the cytoplasm, whereas GFP-HDGF
with a deleted hath region (HDGFnonHATH) was found only in the nucleus.
Exogenously supplied GFP-HDGF was internalized and translocated to the
nucleus. GFP-HATH was internalized, whereas GFP-HDGFnonHATH was not.
Overexpression of HDGF stimulated DNA synthesis and cellular
proliferation, although HDGF with both NLSs deleted did not.
Overexpression of HDGFnonHATH caused a significant stimulation of DNA
synthesis, whereas that of hath protein did not. HDGF containing the
NLS sequence of p53 instead of the bipartite NLS did not stimulate DNA
synthesis, and truncated forms without the C- or N-terminal side of
NLS2 did not. These findings suggest that the gene-specific region, at
least the bipartite NLS sequence and the N- and C-terminal neighboring
portions, is essential for the mitogenic activity of HDGF after nuclear translocation.
Hepatoma-derived Growth Factor Stimulates Cell Growth after
Translocation to the Nucleus by Nuclear Localization Signals*
,,,,,,,,¶
Department of Molecular Medicine, Osaka
University Graduate School of Medicine, and the § Department
of Medical Science I, School of Health and Sport Science, Osaka
University, Yamada-oka 2-2, Suita, Osaka 565-0871, Japan
*
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.
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