Molecular cloning of PC3, a putatively secreted protein whose mRNA is induced by nerve growth factor and depolarization.

Abstract

PC3 is an immediate early gene induced by nerve growth factor in PC12 cells, a cell line derived from a tumor of the adrenal medulla that undergoes neuronal differentiation in the presence of nerve growth factor. This induction is independent of new protein synthesis as it can occur in the presence of cycloheximide. PC3 is also induced with similar kinetics, but at lower levels, by membrane depolarization (both in vivo and in vitro) and epidermal growth factor. It is induced at much lower levels by fibroblast growth factor and interleukin 6. In vivo it is found expressed in tissues, such as brain at embryonic day 13.5, placenta, amnion, and spleen, which are proliferating and/or differentiating. The deduced protein sequence from the cDNA indicates the presence of a signal peptide, suggesting that PC3 is secreted.

ANA, a novel member of Tob/BTG1 family, is expressed in the ventricular zone of the developing central nervous system

“…Inspection of the deduced amino acid sequence of the ANA gene product (ANA) revealed its signi®cant homology at the amino-terminal half (residues 1 ± 115) to the corresponding portions of BTG1 (36% identical, Rouault et al, 1992), PC3 (38%, Bradbury et al, 1991), Tob (31%, Matsuda et al, 1996), and the Xenopus B9 protein (57%, Genbank) (Figure 1c and d). Therefore, we concluded that ANA is a member of Tob/BTG1 family antiproliferative proteins.…”

“…The tob gene, together with the btg1 and pc3/tis21/ btg2 genes, forms a new antiproliferative gene family (Matsuda et al, 1996;Rouault et al, 1992Rouault et al, , 1996Bradbury et al, 1991;Fletcher et al, 1991). Both the BTG1 and Tob proteins suppress growth of NIH3T3 cells when overexpressed (Matsuda et al, 1996;Rouault et al, 1992).…”

Btg1 and Btg2 gene expression during early chick development

“…It is known that BTG2 is induced by NGF, FGF, IL-6, TPA, serum, EGF, and cAMP (Bradbury et al, 1991;Fletcher et al, 1991;Montagnoli et al, 1996) indicating that a number of stimuli triggering different transduction pathways can activate the transcription of this gene. Also Btg1 has been shown to be a direct target of different molecules, including T3 hormone (Rodier et al, 1999), Insuline-like Growth Factor 1 (IGF-1) (Vadgama et al, 2006), or FoxO3A (Bakker et al, 2004).…”

“…Also, a structurally related gene has been characterized in amphioxus, the AmphiTOB gene (Holland et al, 1997). In vertebrates, the whole family is composed of at least six members that have been named differently in different species: Btg1, Btg2 (Tis21 in mouse and PC3 in rat), Btg3 (also named ANA for Abundant in Neuroepithelium Area), Btg4 (PC3B), Tob (Tob1), and Tob2 (Bradbury et al, 1991;Fletcher et al, 1991;Matsuda et al, 1996;Rouault et al, 1996;Guehenneux et al, 1997;Yoshida et al, 1998;Ikematsu et al, 1999). It has been proposed to name the family as APRO (AntiPROliferative) (Matsuda et al, 2001), but most studies and genetic databases continue using the BTG/Tob nomenclature, which will be adopted in this report.…”

“…The Btg2 gene was the first member to be identified, as an immediate response gene in mouse and rat, in two different cellular contexts. The mouse gene was isolated in TPA stimulated NIH 3T3 fibroblasts and was named Tis21 (for TPA-induced sequence) (Fletcher et al, 1991), whereas the rat homologue was isolated as an immediate response gene to NGF stimulation in neural crestderived PC12 cells (Bradbury et al, 1991). Shortly after, the human Btg1 (B-cell-translocation gene 1) was cloned from a chromosomal translocation observed in a lymphoid malignancy (Rouault et al, 1992).…”