학술논문

Identification of a Novel Peroxisome Proliferator Responsive cDNA Isolated from Rat Hepatocytes as the Zinc-Finger Protein ZFP-37
Document Type
Article
Source
Toxicology and Applied Pharmacology; September 1998, Vol. 152 Issue: 1 p107-118, 12p
Subject
Language
ISSN
0041008X; 10960333
Abstract
The implementation of a rat hepatocyte model system and differential display-polymerase chain reaction resulted in the isolation of ZFP-37 as a peroxisome proliferator-responsive gene. In addition to being responsive to peroxisome proliferators, rat ZFP-37 (rZFP-37) mRNA accumulates rapidly after treating cells with several other hepatic tumor promoters, serum, and cycloheximide, indicating that this gene belongs to the immediate-early growth responsive gene family. AlthoughrZFP-37and mouse ZFP-37 (mZFP-37) are both members of the Krüppel-associated box and C2H2zinc finger superfamily of proteins, there are several features that distinguish the two proteins. The primary protein sequences of rat and mouse ZFP-37 are highly conserved, especially within the region encoding the 12 C2H2zinc finger motifs; however, a region believed to be involved in DNA binding inmZFP-37is divergent inrZFP-37.Mouse ZFP-37 mRNA is expressed almost exclusively in testes and brain, whereasrZFP-37mRNA is expressed in testes, brain, kidney, spleen, thymus, lung, and at low levels in liver. A major difference between regulation of ZFP-37 in the two species exists asrZFP-37is induced, whilemZFP-37is repressed, in liver by the administration of the potent peroxisome proliferator Wy 14,643. Despite the fact thatmZFP-37is believed to be important in cell growth and differentiation in testes and brain, the pronounced differences in regulation of this gene in two closely related species preclude an extrapolation torZFP-37's biological role. Nonetheless, the effects of tumor promoters and mitogens on its expression and the inclusion ofrZFP-37into the immediate-early growth gene families raise the possibility that this gene plays a role in hepatocyte proliferation and/or differentiation.