CROSS-COUPLING OF THE NF-THETA-B P65 AND FOS JUN TRANSCRIPTION FACTORS PRODUCES POTENTIATED BIOLOGICAL FUNCTION

NF-kappaB and AP-1 represent distinct mammalian transcription factors that target unique DNA enhancer elements. The heterodimeric NF-kappaB complex is typically composed of two DNA binding subunits, NF-kappaB p50 and NF-kappaB p65, which share structural homology with the c-rel proto-oncogene product. Similarly, the AP-1 transcription factor complex is comprised of dimers of the c-fos and c-jun proto-oncogene products or of closely related proteins. We now demonstrate that the bZIP regions of c-Fos and c-jun are capable of physically interacting with NF-kappaB p65 through the Rel homology domain. This complex of NF-kappaB p65 and Jun or Fos exhibits enhanced DNA binding and biological function via both the kappaB and AP-1 response elements including synergistic activation of the 5' long terminal repeat of the human immunodeficiency virus type 1. These findings support a combinatorial mechanism of gene regulation involving the unexpected cross-coupling of two different classes of transcription factors to form novel protein complexes exhibiting potentiated biological activity.