30 Dangerous Liaisons: Fos and Jun, Oncogenic Transcription Factors

Abstract

OVERVIEW
The oncogenes fos and jun encode proteins that belong to a class of transcription factors characterized by a leucine zipper dimerization domain and an amino-terminally adjacent DNA-binding domain, rich in basic amino acids. Together with the Jun-related proteins, JunB and JunD, and Fos family proteins, Fra1 and FosB, Jun and Fos are major components of the transcriptional regulator AP-1. Jun proteins can form homodimers but more avidly dimerize with Fos and its relatives to bind to the consensus sequence TGACTCA. Fos and Jun can also dimerize with members of the cAMP responsive element binding (CREB) protein family; these heterodimers have a preferential affinity for the CRE consensus sequence TGACGTCA. Jun also interacts with the glucocorticoid receptor, affecting hormone-dependent transcriptional regulation.

Besides the well-defined dimerization and DNA contact surfaces, both Jun and Fos proteins contain less well delineated transcriptional activator domains. For Fos, two such domains have been identified, an acidic region and a proline-rich region. Jun contains a major aminoterminal trans-activation domain, encompassing strongly acidic regions. A second glutamine/proline-rich region adjacent to the DNA-binding domain may affect transcriptional activation indirectly.

jun and fos have strong oncogenic potential that is particularly evident when these genes are transduced by retroviruses. The fos oncogene shows a pronounced tropism for osteogenic target cells in vivo. jun transforms primarily fibroblasts. For fos, the minimal oncogenic domain includes only the DNA-binding and dimerization regions. For jun, it also encompasses the major trans-activator domain. Cellular fos or jun can transform cells in culture, but the viral...