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肝癌衍生生長因子之PWWP/HATH作用區進入細胞的機制探討
Thesis

肝癌衍生生長因子之PWWP/HATH作用區進入細胞的機制探討

廖方瑜
Masters, 國立清華大學, 生物資訊與結構生物研究所
2005

Abstract

HATH作用區 內吞作用 HDGF HATH domain internalization HDGF
HDGF (hepatoma-derived growth factor) is a novel growth factor, identified from conditioned medium of hepatoma cell line. HDGF has growth stimulating activity for fibroblast and some hepatoma cells. HDGF, a novel defined growth factor with mitogenic effect, has homology protein sequence as HMG (high mobility group) protein and their three dimension structures appeared to be similar to each other. Recently, elevated HDGF expression was found in developing kidneys but less was found in adult kidney. In addition, HDGF expression was found to be correlated with angiogenic status of tissues. Thus, it is speculated that HDGF plays a role during embryonic development and angiogenesis. HDGF also plays a role in cell-cell interaction and cell migration. HDGF is a growth factor that is involved in stimulating vascular smooth muscle cells (SMCs) proliferation during development and in disease. HDGF contains a true bipartite nuclear localization sequence necessary for nuclear targeting. HDGF is sciential factor in stimulating of DNA replication and cell proliferation of vascular smooth muscle cell. Here, we investigate the NIH 3T3 cells internalization mechanism of the HATH domain of HDGF. We found HATH domain internalization is dynamin-independent. By using confocal microscopy, we show that HATH domain was colocalized with Dextran. The different mechanisms of uptake and cellular processing were studied by treating with macropinocytosis pathway inhibitor to investigate HATH domain internalization. Since these inhibitors can block HATH domain uptake, we suggest that the internalization mechanism of HATH domain may be similar to macropinocytosis.

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