Lm. Scearce et al., RNR-1, A NUCLEAR RECEPTOR IN THE NGFI-B NUR77 FAMILY THAT IS RAPIDLY INDUCED IN REGENERATING LIVER, The Journal of biological chemistry, 268(12), 1993, pp. 8855-8861
Liver regeneration following partial hepatectomy provides one of the f
ew systems for analysis of mitogenesis in the fully developed, intact
animal. Immediate-early growth response genes, induced in the absence
of prior protein synthesis, play an important regulatory role in the r
egenerative process. During screening of a subtracted cDNA library of
immediate-early genes induced during liver regeneration, a novel membe
r of the thyroid/steroid receptor superfamily, RNR-1 (regenerating liv
er nuclear receptor), was identified. This gene is not expressed in qu
iescent liver but is rapidly induced following partial hepatectomy and
is specific to hepatic growth as it is not induced in other mitogen-t
reated cells. RNR-1 is also expressed in brain. A full-length cDNA clo
ne of RNR-1 encodes a 66-kDa, 597-amino acid protein as verified by in
vitro translation in reticulocyte lysate. RNR-1 is highly homologous
to r-NGFI-B/m-Nur77 particularly in the DNA binding (94%) and putative
ligand binding (59%) domains. Using a mobility shift assay, we have s
hown that RNR-1 specifically binds to the NGFI-B DNA half-site and for
ms a complex very similar in size to the Nur77 complex, suggesting tha
t RNR-1 also may bind as a monomer. Consistent with this finding, the
A box region important in mediating half-site binding is 100% conserve
d between r-NGFI-B/m-Nur77. Both RNR-1 and Nur77 strongly transactivat
e a reporter driven by a consensus r-NGFI-B/Nur77 binding site, and th
eir effect together is additive. As both the RNR-1 and r-NGFI/m-nur77
genes are induced during liver regeneration, it is very possible that
RNR-1 acts concomitantly with r-NGFI/m-Nur77 in regulating the express
ion of delayed-early genes during liver regeneration.