I. Introduction THE insulin-like growth factors (IGFs) and their receptors and binding proteins constitute a family of cellular modulators that play essential roles in the regulation of growth and development. The IGF ligands include three structurally related peptides: insulin, IGF-I, and IGF-II. Unlike insulin, IGF-I and IGF-II are expressed ubiquitously, albeit in a highly regulated manner (see reviews in Refs. 1-5). The biological functions of the IGFs are mediated by a family of transmembrane receptors, which includes the insulin, IGF-I, and IGF-II/mannose-6-phosphate (M-6-P) receptors. While the IGF-I receptor is the primary mediator of IGF action, the insulin and IGF-II/M-6-P receptors may also mediate some of these functions (Fig. 1) (6, 7). The biological actions of the IGFs are modulated by a family of at least six IGF-binding proteins (IGFBPs) that are found in the circulation and in extracellular compartments and are produced by most tissues. The IGFBPs are capable of inhibiting or enhancing I...

Molecular and cellular aspects of the insulin-like growth factor I receptor

The mechanism by which a single factor evokes opposite regulatory effects from a specific DNA sequence is not well understood. In this study, a 25-base pair element that resides upstream of the mouse proliferin gene was examined; it conferred on linked promoters either positive or negative glucocorticoid regulation, depending upon physiological context. This sequence, denoted a "composite" glucocorticoid response element (GRE), was bound selectively in vitro both by the glucocorticoid receptor and by c-Jun and c-Fos, components of the phorbol ester-activated AP-1 transcription factor. Indeed, c-Jun and c-Fos served as selectors of hormone responsiveness: the composite GRE was inactive in the absence of c-Jun, whereas it conferred a positive glucocorticoid effect in the presence of c-Jun, and a negative glucocorticoid effect in the presence of c-Jun and relatively high levels of c-Fos. The receptor also interacted selectively with c-Jun in vitro. A general model for composite GRE action is proposed that invokes both DNA binding and protein-protein interactions by receptor and nonreceptor factors.

https://science.sciencemag.org/content/sci/249/4974/1266.full.pdf

Transcription factor interactions: selectors of positive or negative regulation from a single DNA element.

https://www.imt.uni-marburg.de/suske/pdf/Gene_238_291.pdf

The Sp-family of transcription factors

Compilation of vertebrate-encoded transcription factors.

Transcription factors, normal myeloid development, and leukemia.

The expression of the trans-acting transcription factor Sp1 in mice was defined by a combination of RNA analysis and immunohistochemical localization of the Sp1 protein. Although ubiquitously expressed, there was an unexpected difference of at least 100-fold in the amount of Sp1 message in different cell types. Sp1 protein levels showed corresponding marked differences. Substantial variations in Sp1 expression were also found in some cell types at different stages of development. Sp1 levels appeared to be highest in developing hematopoietic cells, fetal cells, and spermatids, suggesting that an elevated Sp1 level is associated with the differentiation process. These results indicate that Sp1 has a regulatory function in addition to its general role in the transcription of housekeeping genes.

Developmental expression of Sp1 in the mouse.

Expression of the trans-acting transcription factor Sp1 increased almost 10-fold after infection of cells by simian virus 40. This alteration, attributable to an early viral protein, occurred at the mRNA level beginning at 12 hr postinfection, shortly after the appearance of viral T antigen, and reached a plateau at 20 hr postinfection. The enhanced level of Sp1 message was accompanied by a marked increase in Sp1 protein in the cell nuclei. Furthermore, we have demonstrated that stimulation of Sp1 levels elevates expression from viral and cellular promoters. Enhancing the amount of this trans-acting factor may play a role in aiding the viral life cycle and in neoplastic transformation of infected cells.

/pdf/sv40-stimulates-expression-of-the-transacting-factor-sp1-at-1rgw3pr3tv.pdf

J D Saffer

Papers

Developmental expression of Sp1 in the mouse.

SV40 stimulates expression of the transacting factor Sp1 at the mRNA level.