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Expression and regulation of ERp57 in hepatocellular carcinoma
Author(s) -
Grindel Brian J.,
FarachCarson Mary Cindy,
Bennett Joseph,
Snapp Erik
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.826.2
Subject(s) - cytoplasm , cytosol , nucleus , subcellular localization , endoplasmic reticulum , transcription factor , cell nucleus , microbiology and biotechnology , green fluorescent protein , nuclear localization sequence , chemistry , cell , nuclear transport , biology , biochemistry , gene , enzyme
ERp57/PDIA3, a 1,25D 3 binding protein with thiol‐oxidoreductase activity, resides in the endoplasmic reticulum (ER) owing to a C‐terminal QEDL. ERp57 partitions among cell surface, cytoplasm and nucleus with functions including 1,25D 3 binding, ion transport, and redox modulation of transcription. A tissue array immunoscreen of normal and diseased liver sections showed dynamic changes in expression in both cytoplasm and nucleus. To understand expression of ERp57 in hepatocellular carcinoma (HCC), its steady state distribution was assessed in HepG2 cells using: 1) GFP (green fluorescent protein) tagged ERp57 and, 2) subcellular fractionation. We also measured the response to various treatments including PMA, 1,25D 3 , or TNF‐α. High resolution imaging demonstrates localization of ERp57‐GFP in the ER along with additional peri‐nuclear staining. A small (<5%) fraction of ERp57 also exists in the cytosol. Co‐treatment with PMA, alone and in combination with 1,25D 3 for times from 15′ to 1 h did not reorganize EPp57‐GFP. In contrast, TNF‐α treatment of HepG2 cells moved cytoplasmic ERp57‐GFP to the nucleus in 15 min. Ongoing studies will determine if ERp57 binds to NFκB in HepG2 cells or in normal hepatocytes after TNF‐α treatment. These studies will shed light on redox regulation of transcription by nuclear ERp57 during TNF‐α signaling in normal and transformed liver cells. Supported by HHMI and the CTCR‐UD.