Both products of the fosB gene, FosB and its short form, FosB/SF, are transcriptional activators in fibroblasts.

Abstract

We demonstrate that a member of thefos family, thefosB gene, gives rise to two transcripts by alternative splicing of exon 4, generating two proteins, FosB of 338 amino acids and a short form, FosB/SF, which contains the DNA binding and dimerization domains but not the 101 amino acids of the C terminus. FosB/SF activates an AP-1-chloramphenicol acetyltransferase construct in NIH 3T3 cells, as determined by transient and stable transfections, although more weakly than does FosB. In contrast to FosB, FosB/SF has lost its ability to repress the dyad symmetry element of the c-fos gene. FosB/SF when expressed in excess to FosB can downmodulate the activity of FosB. Constitutive expression of high levels of FosB/SF in NIH 3T3 cells has no significant inhibitory effect in the induction of cell proliferation or cell cycle progression, indicating that FosB/SF is not a negative regulator of cell growth. This conclusion is further confirmed by the observation that the majority of the Jun molecules are complexed with FosB/SF in the FosB/SF-overexpressing cells.

Absence of a Persistently Elevated 37 kDa Fos-Related Antigen and AP-1-Like DNA-Binding Activity in the Brains of Kainic Acid-TreatedfosB Null Mice

“…To investigate whether this protracted induction resulted from transcriptional processes, we examined the expression of fosB mRNA in wild-type mice using in situ hybridization. fosB and ⌬-fosB transcripts differ only by the deletion of an internal 140 base segment (exon 4) in the latter (Dobrzanski et al, 1991;Mumberg et al, 1991;Nakabeppu and Nathans, 1991;Yen et al, 1991). Therefore, we implemented an in situ paradigm that could differentiate the expression of fosB from ⌬-fosB.…”

“…Moreover, based upon supershift and immunoblot analyses, these AP-1 complexes appear to be heterodimers of JunD in association with a series of proteins in the range of 35-37 kDa that cross-react with antisera to FosB (Hope et al, 1994b;Chen et al, 1995). While these proteins have physical and immunological properties consistent with the splice variant of FosB, termed ⌬-FosB (Dobrzanski et al, 1991;Mumberg et al, 1991;Nakabeppu and Nathans, 1991;Yen et al, 1991), their precise identity remains uncertain. Some of this ambiguity stems from the fact that while fosB mRNA is induced during the acute response to a stimulus, it is not chronically elevated (Chen et al, 1995;Kasof et al, 1995).…”

Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins.

“…However, the binding affinity and transcriptional activation of the Jun proteins are dramatically increased upon dimerization with Fos proteins (6,9,23,28,29,33,39,42). The complexity arising from the possible associations between different Jun and Fos proteins has been further increased by the findings that Fos proteins differentially affect the activity of the Jun proteins (7,33,39). Interestingly, the members of the jun (16, [30][31][32]34) and fos (5,8,15,20,22,26,42) families belong to the set of genes that are rapidly induced by growth factors in quiescent fibroblasts (3,10,17), indicating that the Jun and Fos proteins may play an important role in the regulation of cellular proliferation.…”

Opposing activities of c-Fos and Fra-2 on AP-1 regulated transcriptional activity in mouse keratinocytes induced to differentiate by calcium and phorbol esters

“…The Fos proteins contribute distinct functions towards the activity of the AP-1 heterodimer. For example, c-Fos can both activate and repress transcription (Gius et al, 1990), the full-length Fos B is a transcriptional activator (Dobrazanski et al, 1991) and a naturally occurring short form of Fos B inhibits AP-1 transactivation (Yen et al, 1991;Nakabeppu and Nathans, 1991). The Fos-related antigens Fra-1 and Fra-2 lack functional transactivation domains and are poor transcriptional activators (Gius et al, 1990;Yoshioka et al, 1995;Suzuki et al, 1991).…”