Cell Growth & Differentiation, Vol 3, Issue 12 889-897, Copyright © 1992 by American Association of Cancer Research

ARTICLES

Heterodimerization with c-Fos is not required for cell transformation of chicken embryo fibroblasts by Jun

M Hughes, A Sehgal, M Hadman and T Bos
Department of Microbiology and Immunology, Eastern Virginia Medical School, Norfolk 23501.

c-Jun belongs to a family of proteins that require dimerization for activity. Dimerization occurs through a leucine-rich region near the carboxy terminus called the leucine zipper. Jun can form dimeric complexes with other Jun family as well as Fos family members. The relative proportion of these different dimeric complexes is determined by the relative abundance of each family member at a particular time. Overexpression of v-Jun or c-Jun alone will lead to cell transformation of chicken embryo fibroblasts, albeit with varying efficiencies. Upon overexpression, v-Jun or c-Jun presumably becomes the predominant AP-1 component in the cell. Theoretically, this should lead to a larger proportion of homodimers than heterodimers. It is not clear what role, if any, the other Jun and Fos family proteins play during cell transformation. We have examined the ability of Jun to induce cell transformation in chicken embryo fibroblasts in the absence of interaction with other Jun or Fos family proteins. To this end, we have constructed a chicken v-Jun mutant that is incapable of heterodimerization. This was accomplished by replacing the leucine zipper region of Jun with that of the yeast transcription factor GCN4. This chimeric protein, VJ-GLZ, retains all of the DNA binding and transcriptional activation domains of v-Jun. As expected, in vitro translated VJ-GLZ was found to be incapable of forming heterodimers with c-Fos, FosB, and JunD.(ABSTRACT TRUNCATED AT 250 WORDS)

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