TY - JOUR
T1 - Identification of a novel peroxisome proliferator responsive cDNA isolated from rat hepatocytes as the zinc-finger protein ZFP-37
AU - Vanden Heuvel, John P.
AU - Holden, Peter
AU - Tugwood, Jonathan
AU - Ingle, Christine
AU - Yen, Weiyi
AU - Galjart, Niels
AU - Greenlee, William F.
PY - 1998/9
Y1 - 1998/9
N2 - 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. Although rZFP-37 and mouse ZFP-37 (mZFP-37) are both members of the Kruppel-associated box and C2H2 zinc 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 C2H2 zinc finger motifs; however, a region believed to be involved in DNA binding in mZFP-37 is divergent in rZFP-37. Mouse ZFP-37 mRNA is expressed almost exclusively in testes and brain, whereas rZFP-37 mRNA 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 as rZFP-37 is induced, while mZFP-37 is repressed, in liver by the administration of the potent peroxisome proliferator Wy 14,643. Despite the fact that mZFP-37 is 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 to rZFP-37's biological role. Nonetheless, the effects of tumor promoters and mitogens on its expression and the inclusion of rZFP-37 into the immediate-early growth gene families raise the possibility that this gene plays a role in hepatocyte proliferation and/or differentiation.
AB - 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. Although rZFP-37 and mouse ZFP-37 (mZFP-37) are both members of the Kruppel-associated box and C2H2 zinc 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 C2H2 zinc finger motifs; however, a region believed to be involved in DNA binding in mZFP-37 is divergent in rZFP-37. Mouse ZFP-37 mRNA is expressed almost exclusively in testes and brain, whereas rZFP-37 mRNA 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 as rZFP-37 is induced, while mZFP-37 is repressed, in liver by the administration of the potent peroxisome proliferator Wy 14,643. Despite the fact that mZFP-37 is 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 to rZFP-37's biological role. Nonetheless, the effects of tumor promoters and mitogens on its expression and the inclusion of rZFP-37 into the immediate-early growth gene families raise the possibility that this gene plays a role in hepatocyte proliferation and/or differentiation.
UR - http://www.scopus.com/inward/record.url?scp=0031793057&partnerID=8YFLogxK
U2 - 10.1006/taap.1998.8478
DO - 10.1006/taap.1998.8478
M3 - Article
C2 - 9772206
AN - SCOPUS:0031793057
SN - 0041-008X
VL - 152
SP - 107
EP - 118
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 1
ER -