The role of c-Fos in the regulation of the JC virus gene transcription

Thu, 04/20/2017 - 11:10

c-Fos is a member of the AP-1 transcription factor family under the Fos protein family umbrella, alongside Fra-1, Fra-2 and Fos-B.  Also in the AP-1 transcription family are the Jun proteins, c-Jun, Jun-B and Jun-D.  Each member of the AP-1 transcription family is a phosphonuclear protein composed of a carboxy-terminal leucine zipper domain, a basic domain and an amino terminal transactivation domain. Together the Fos and Jun families compose a dimeric complex that binds to response elements on DNA in order to regulate gene expression, cell proliferation, cell differentiation, tumorigenesis and more.  Their induction can be catalyzed by a number of signals, including cytokines and growth factors, stress and viral infection.  Interestingly, c-Fos was first characterized as part of a DNA binding protein complex in the simian virus gene (SV40).  The JC virus (JCV) is a human polyomavirus that is a pre-cursor for the demyelinating disease progressive multifocal leukoencephalopathy (PML).  Using a c-Fos antibody in PML and JCV research helps researchers to better understand the role of AP-1 transcription factors in their pathogenesis.

c-Fos antibody

c-Fos Antibody [NBP1-89065] - Staining of human adrenal gland shows strong nuclear and cytoplasmic positivity in cortical cells.

First, Kim et al used a c-Fos antibody to show that c-Jun and c-Fos functionally interact with the JC Virus early regulatory protein Large T Antigen.  To begin, Kim et al established that c-Jun and c-Fos suppressed T-Ag-mediated viral DNA replication using a reported plasmid containing the JCV gene transfected into U-87MG cells containing c-Fos or c-Jun expression plasmids.  Next, a c-Fos antibody was used to show that c-Jun and c-Fos physically interact with T-Ag in a GST pull-down assay using nuclear extracts from U-87MG cells. Further research is required in order to better understand whether c-Fos and c-Jun act together or independently of one another to regulate this antigen.

Another use of the c-Fos antibody in JCV research comes from Sadowska et al in their research of the regulation of JCV gene transcription by the AP-1 complex in glial cells.  Similar to Kim et al, Sadowska first established an interaction between AP-1 proteins and the JCV promoter using DNA band shift assays.  A co-transfection experiment on c-Jun and c-Fos further confirmed that these proteins do activate transcription of the JCV promoter as well.  While Sadowska did find that the binding site between JCV and AP-1 responds to activation by either c-Jun or c-Fos, western blot analysis using a c-Jun antibody was used to confirm that c-Jun levels are modulated during the viral infection cycle. 

View c-Fos antibodies for your research.

  1. Sadowska B, Barrucco R, Khalili K, Safak M. Regulation of human polyomavirus JC virus gene transcription by AP-1 in glial cells. [PMID: 12477869]
  2. Kim J, Woolridge S, Biffi R, Borghi E, Lassak A, Ferrante P, Amini S, Khalili K, Safak M. Members of the AP-1 family, c-Jun and c-Fos, functionally interact with JC virus early regulatory protein large T antigen. [PMID: 12692226]
  3. Kharman-Biz A, Gao H, Ghiasvand R, Zhao C, Zendehdel K, Dahlman-Wright K. Expression of activator protein-1 (AP-1) family members in breast cancer. [PMID: 24073962]

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