An alternative spliced form of FosB is a negative regulator of transcriptional activation and transformation by Fos proteins.

Abstract

Two forms of FosB transcript and their products can be identified in mouse NIH 3T3 cells following serum induction. The larger RNA codes for a 338-amino acid protein, whereas the smaller RNA results from the removal of an additional 140 nucleotides from FosB mRNA by alternative splicing. This alternative splicing event places a stop codon following the "leucine zipper" region and results in a shorter protein (FosB2) of 237 amino acids that lacks 101 amino acids at the carboxyl terminus. FosB2 is able to form heterodimers with c-Jun and bind to an AP-1 site but is not able to activate the transcription of promoters containing AP-1 sites. Furthermore, FosB2 can not only suppress the transcriptional activation by c-Fos and c-Jun of promoters containing an AP-1 site but also interferes with the transforming potential of viral and cellular Fos proteins. We propose that FosB2 protein functions as a trans-negative regulator.

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).…”

Transcriptional mechanisms of addiction: role of ΔFosB

“…DFosB binds to Jun family members and the resulting dimer binds AP-1 sites in DNA. Some in vitro studies suggest that because DFosB lacks much of its transactivation domain, it functions as a negative regulator of AP-1 activity, while several others show that DFosB can activate transcription at AP-1 sites (Dobrazanski et al 1991;Nakabeppu & Nathans 1991;Yen et al 1991;Chen et al 1997). …”

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).…”