The serum-inducible mouse gene Krox-24 encodes a sequence-specific transcriptional activator.

Abstract

The mouse gene Krox-24 is transiently activated during cell cycle reentry. It encodes a protein with three zinc fingers similar to those of the transcription factor Sp1. Here we present a biochemical characterization of the gene products. Krox-24 mRNA is translated into two proteins of 82 and 88 kilodaltons, designated p82Krox-24 and p88Krox-24, respectively. p82Krox-24 is initiated at the first AUG codon of the open reading frame, whereas synthesis of p88Krox-24 starts at a non-AUG codon located upstream. Both proteins were synthesized in HeLa cells infected with recombinant vaccinia viruses expressing Krox-24 cDNAs. Under these conditions, they were found phosphorylated on serine residues and glycosylated. The availability of the proteins made possible the determination of the DNA recognition sequence. In vitro, Krox-24 bound specifically to the sequence 5'-GCG(C/G)GGGCG-3'. This sequence is similar but not identical to the Sp1 target sequence. Insertion of an oligomer for the binding site in cis, close to the herpes simplex virus thymidine kinase promoter, rendered this promoter responsive to Krox-24. Krox-24 is therefore a sequence-specific transcriptional activator. Krox-24-binding sites were found upstream of several serum-inducible genes, raising the possibility that Krox-24 is involved in the regulation of these genes.

Basic fibroblast growth factor transcriptional autoregulation requires EGR-1

“…Our data presented here indicate that a critical downstream e ector of bFGF function is the Egr-1 transcription factor. Activation of Egr-1 is suggested to be involved in the regulation of the G 0 /G 1 transition in mammalian cells (Lemaire et al, 1990). Besides bFGF, Egr-1 also targets many other growth factors and growth factor receptors such as PDGF-A, B (Khachigian et al, 1995(Khachigian et al, , 1996, tissue factor (Cui et al, 1996) and possibly epidermal growth factor receptor, suggesting that activation of Egr-1 may play a common role in the formation of a positive feedback autocrine loop, which is often involved in the mitogenic pathways and transformation.…”

Differential expression of NDF/neuregulin receptors ErbB-3 and ErbB-4 and involvement in inhibition of neuronal differentiation

“…Indeed, concomitant with the characteristic growth arrest, appearance of embryoid bodies, and outgrowth of neurites, RA-treated P19 cultures displayed upregulation of the transcription factor Egr-1. This was evident from an electrophoretic mobility shift assay using a GC-rich consensus DNA sequence, that binds to all members of the Egr family (Figure 6c) (Lemaire et al, 1990). Interestingly, induction of an Egr-like DNA binding activity preceded morphological alterations, but incubation with a relatively high concentration of NDF-b1 rapidly abolished the DNA binding activity of Egr-1.…”

Activation of mitogen-activated protein kinase couples neurotensin receptor stimulation to induction of the primary response gene Krox-24

“…This can be supported by the following points : (1) studies with dominant-negative MAPK have provided evidence that this pathway can lead to the stimulation of DNA synthesis [45], (2) Krox-24 induction is an early response event to all cell division signals examined so far [46][47][48][49], and (3) studies with anti-sense oligonucleotides have demonstrated that the induction of Krox-24 in lymphocytes is necessary for cell proliferation to occur [49,50]. This is presumably accomplished by the induction of a second wave of function-related genes that are controlled by Krox-24.…”