c-Fos antagonizes the junD gene positive autoregulatory loop; a novel c-Fos role in promoter switching.

In contrast to c-jun and junB, the junD gene is constitutively expressed in quiescent cells. The junD promoter, therefore, may provide a paradigm for promoters mostly active in growth arrested cells. We report here that the human junD promoter is repressed by serum and TPA. Also, the ability of JunD to positively autoregulate its promoter is abolished under these conditions. The obtained promoter repression depends on the junD promoter TRE, suggesting the involvement of bZip proteins in this process. We found that c-Fos, a bZip protein known to be induced by serum and TPA, is sufficient to antagonize the JunD function. Furthermore, selective activation of the junD promoter by JunD is abolished by c-Fos with concomitant activation of the collagenase promoter. The latter contains a TRE that is transcriptionally activated in proliferating cells. We propose that c-Fos plays a novel role in intergenic promoter switching, downregulating quiescent-state related genes while simultaneously upregulating proliferation-state specific genes.

[1]  M. Karin,et al.  Phorbol ester-inducible genes contain a common cis element recognized by a TPA-modulated trans-acting factor , 1987, Cell.

[2]  Y. Shaul,et al.  The human junD gene is positively and selectively autoregulated. , 1994, DNA and cell biology.

[3]  M. Yaniv,et al.  Characterization of junD: a new member of the jun proto‐oncogene family. , 1989, The EMBO journal.

[4]  M. Yaniv,et al.  Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras , 1994, Cell.

[5]  R. Tjian,et al.  Purified transcription factor AP-1 interacts with TPA-inducible enhancer elements , 1987, Cell.

[6]  R. Tjian,et al.  Leucine repeats and an adjacent DNA binding domain mediate the formation of functional cFos-cJun heterodimers. , 1989, Science.

[7]  H. Herschman.  Primary response genes induced by growth factors and tumor promoters. , 1991, Annual review of biochemistry.

[8]  D. Nathans,et al.  jun-D: a third member of the jun gene family. , 1989, Proceedings of the National Academy of Sciences of the United States of America.

[9]  D. F. Far,et al.  Cyclic AMP stimulates a JunD/Fra-2 AP-1 complex and inhibits the proliferation of interleukin-6-dependent cell lines. , 1995, Oncogene.

[10]  M. Karin,et al.  Elevation of AP1 activity during F9 cell differentiation is due to increased c-jun transcription. , 1990, The New biologist.

[11]  M. Karperien,et al.  Characterization of the mouse junD promoter‐‐high basal level activity due to an octamer motif. , 1991, The EMBO journal.

[12]  Y. Shaul,et al.  The X protein of hepatitis B virus coactivates potent activation domains , 1995, Molecular and cellular biology.

[13]  M. Getz,et al.  Tissue factor gene transcription in serum-stimulated fibroblasts is mediated by recruitment of c-Fos into specific AP-1 DNA-binding complexes. , 1995, Biochemistry.

[14]  W. Kolch,et al.  Raf revertant cells resist transformation by non-nuclear oncogenes and are deficient in the induction of early response genes by TPA and serum. , 1993, Oncogene.

[15]  Y. Shaul,et al.  A single element within the hepatitis B virus enhancer binds multiple proteins and responds to multiple stimuli , 1990, Journal of virology.

[16]  M. Karin,et al.  The role of Jun, Fos and the AP-1 complex in cell-proliferation and transformation. , 1991, Biochimica et biophysica acta.

[17]  S. Berger,et al.  Selective inhibition of activated but not basal transcription by the acidic activation domain of VP16: Evidence for transcriptional adaptors , 1990, Cell.

[18]  R. Bravo,et al.  c-JUN, JUN B, and JUN D differ in their binding affinities to AP-1 and CRE consensus sequences: effect of FOS proteins. , 1991, Oncogene.

[19]  R. Scott,et al.  JunD phosphorylation, and expression of AP-1 DNA binding activity modulated by serum growth factors in quiescent murine 3T3T cells. , 1996, Oncogene.

[20]  P. Vogt,et al.  The chicken junD gene and its product. , 1991, Oncogene.

[21]  J. Visvader,et al.  Fos-Jun interaction: mutational analysis of the leucine zipper domain of both proteins. , 1989, Genes & development.

[22]  Y. Shaul,et al.  Structure and function of human jun-D. , 1991, Oncogene.

[23]  M. Karin,et al.  Different requirements for formation of Jun: Jun and Jun: Fos complexes. , 1989, Genes & development.

[24]  L. Kaczmarek,et al.  Visual Stimulation Regulates the Expression of Transcription Factors and Modulates the Composition of AP-1 in Visual Cortexa , 1996, The Journal of Neuroscience.

[25]  J. Ortonne,et al.  Mitogen-activated Protein Kinase Pathway and AP-1 Are Activated during cAMP-induced Melanogenesis in B-16 Melanoma Cells (*) , 1995, The Journal of Biological Chemistry.

[26]  M. Comb,et al.  cAMP-dependent regulation of proenkephalin by JunD and JunB: positive and negative effects of AP-1 proteins. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[27]  Y. Shaul,et al.  Functional organization of the hepatitis B virus enhancer , 1990, Molecular and cellular biology.

[28]  T. Kouzarides,et al.  The role of the leucine zipper in the fos–jun interaction , 1988, Nature.

[29]  M. Karin,et al.  Jun-B differs in its biological properties from, and is a negative regulator of, c-Jun , 1989, Cell.

[30]  T. Toda,et al.  A new group of conserved coactivators that increase the specificity of AP-1 transcription factors , 1996, Nature.

[31]  H. Iba,et al.  Difference in transcriptional regulatory function between c-Fos and Fra-2. , 1991, Nucleic acids research.

[32]  T. Curran,et al.  Parallel association of Fos and Jun leucine zippers juxtaposes DNA binding domains. , 1989, Science.

[33]  C. Powers,et al.  Modulation of JunD·AP-1 DNA Binding Activity by AP-1-associated Factor 1 (AF-1)* , 1996, The Journal of Biological Chemistry.

[34]  P. Gass,et al.  Basal expression of the inducible transcription factors c‐Jun, JunB, JunD, c‐Fos, FosB, and Krox‐24 in the adult rat brain , 1995, The Journal of comparative neurology.