A modified version of a Fos-associated cluster in HBZ affects Jun transcriptional potency.
Like c-Fos, HBZ (HTLV-I bZIP factor) is able to interact with c-Jun but differs considerably from c-Fos in its ability to activate AP-1-responsive genes since HBZ rather inhibits transcriptional activity of c-Jun. To better understand the molecular mechanisms involved in this down-regulation of c-Jun activity, a large number of HBZ/c-Fos chimeras was constructed and analyzed for their ability to interact with c-Jun, to bind to the AP-1 motif and to stimulate expression of a reporter gene containing the collagenase promoter. By this approach, we demonstrate that the DNA-binding domain of HBZ is responsible for its inhibitory effect on the trans-activation potential of c-Jun. However, unexpectedly, we found that exchange of a cluster of six charged amino acids immediately adjacent to the DNA contact region altered significantly transcriptional activity of chimeras. This particular subdomain could be involved in efficient presentation of the AP-1 complex to the transcriptional machinery. To confirm this role, specific residues present in the cluster of HBZ were substituted for corresponding amino acids in c-Fos. Unlike the JunD-activating potential of wild-type HBZ, this mutant was no longer able to stimulate JunD activity, confirming the key role of this particular cluster in regulation of Jun transcriptional potency.
Hivin
Patrick
P
Laboratoire Infections Rétrovirales et Signalisation Cellulaire, CNRS/UM I UMR 5121/IFR 122, Institut de Biologie, 34000, Montpellier, France.
Arpin-André
Charlotte
C
Clerc
Isabelle
I
Barbeau
Benoit
B
Mesnard
Jean-Michel
JM
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D005786:Gene Expression Regulation; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D016760:Proto-Oncogene Proteins c-fos / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D012191:Retroviridae Proteins; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
D050976:Basic-Leucine Zipper Transcription Factors; C479751:HBZ protein, human T-cell leukemia virus type I; D016760:Proto-Oncogene Proteins c-fos; D016755:Proto-Oncogene Proteins c-jun; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D012191:Retroviridae Proteins; D014764:Viral Proteins