fosB is a transforming gene encoding a transcriptional activator - PubMed (original) (raw)

Affiliations

PMID: 1903195

fosB is a transforming gene encoding a transcriptional activator

M Schuermann et al. Oncogene. 1991 Apr.

Abstract

The fosB gene encodes a nuclear protein that shows a high degree of homology with c-Fos in several of the known functionally crucial domains, e.g., the leucine zipper and the DNA-binding site, but shows considerable divergence in other regions. Here, we report that FosB, when placed under the control of a constitutive promoter, exhibits clear transforming properties in focus assays using mouse NIH3T3 or rat 208F fibroblasts. The transforming potential of FosB is considerably stronger than that of a corresponding c-fos construct and resembles that of viral fos genes. Using chimeric fos/fosB constructs we show that the C-terminal half of FosB is responsible for these stronger transforming properties, apparently by giving rise to significantly higher levels of protein as compared with the corresponding c-fos sequence. Surprisingly, substitution of the N-terminus of Fos with that of FosB decreases its transforming potential. These differences in the transforming potential are not related to DNA or protein expression, but rather seem to reflect differences in the molecular function(s) encoded in the N-terminal halves of Fos and FosB protein. Both, fosB- and v-fos transformed cells show increased expression of a number of endogenous genes, including c-jun, transin, alpha 1(III) collagen and tissue plasminogen activator. Transactivation by FosB and v-fos of the c-jun and alpha 1(III) collagen gene promoters and of a 3 x TRE-tk chimeric promoter could be shown in transient CAT assays. v-Fos, but not FosB-transformed cells, also show elevated levels of urokinase and plasminogen activator inhibitor mRNAs, pointing to potential differences in the gene regulatory properties of the two Fos family members.

PubMed Disclaimer

Cited by

The Mos/MAP kinase pathway stabilizes c-Fos by phosphorylation and augments its transforming activity in NIH 3T3 cells.
Okazaki K, Sagata N. Okazaki K, et al. EMBO J. 1995 Oct 16;14(20):5048-59. doi: 10.1002/j.1460-2075.1995.tb00187.x. EMBO J. 1995. PMID: 7588633 Free PMC article.
Proto-oncogene FosB: the amino terminus encodes a regulatory function required for transformation.
Wisdom R, Verma IM. Wisdom R, et al. Mol Cell Biol. 1993 May;13(5):2635-43. doi: 10.1128/mcb.13.5.2635-2643.1993. Mol Cell Biol. 1993. PMID: 8474434 Free PMC article.
An autonomous N-terminal transactivation domain in Fos protein plays a crucial role in transformation.
Jooss KU, Funk M, Müller R. Jooss KU, et al. EMBO J. 1994 Mar 15;13(6):1467-75. doi: 10.1002/j.1460-2075.1994.tb06401.x. EMBO J. 1994. PMID: 8137828 Free PMC article.
Existence of different Fos/Jun complexes during the G0-to-G1 transition and during exponential growth in mouse fibroblasts: differential role of Fos proteins.
Kovary K, Bravo R. Kovary K, et al. Mol Cell Biol. 1992 Nov;12(11):5015-23. doi: 10.1128/mcb.12.11.5015-5023.1992. Mol Cell Biol. 1992. PMID: 1406676 Free PMC article.
Absence of a persistently elevated 37 kDa fos-related antigen and AP-1-like DNA-binding activity in the brains of kainic acid-treated fosB null mice.
Mandelzys A, Gruda MA, Bravo R, Morgan JI. Mandelzys A, et al. J Neurosci. 1997 Jul 15;17(14):5407-15. doi: 10.1523/JNEUROSCI.17-14-05407.1997. J Neurosci. 1997. PMID: 9204924 Free PMC article.

fosB is a transforming gene encoding a transcriptional activator - PubMed (original) (raw)