Post by Max on Jul 20, 2005 16:22:21 GMT -5
Inhibition of transcription factor NF-Y through decreased phosphorylation due to CDK inhibition
The transcriptional activator NF-Y is a heterotrimeric complex composed of NF-YA, NF-YB, and NF-YC, which specifically binds the CCAAT consensus present in about 30% of eukaryotic promoters. All three subunits contain evolutionarily conserved core regions, which comprise a histone fold motif (HFM) in the case of NF-YB and NF-YC. In vitro binding studies and nuclear import assays reveal two different transport mechanisms for NF-Y subunits. While NF-YA is imported by an importin beta-mediated pathway, the NF-YB/NF-YC heterodimer is translocated into the nucleus in an importin 13-dependent manner. Importin beta binding is restricted to the monomeric, uncomplexed NF-YA subunit. In contrast, the nuclear import of NF-YB and NF-YC requires dimer formation. Only the NF-YB/NF-YC dimer, but not the monomeric components, are recognized by importin 13 and are imported into the nucleus. Importin 13 competes with NF-YA for binding to the NF-YB/NF-YC dimer. Our data suggest that a distinct binding platform derived from the HFM of both subunits, NF-YB/NF-YC, mediates those interactions [1]. C/EBP homologous protein (CHOP) is retinoid-responsive gene [2].
NF-Y transcription through phosphorylation is CDK dependant [3], in a similiar manner to transcription of Sp1 via phosphorylation. Sp1 and NF-Y are ubiquitously expressed. In retinoic acid regulation of several genes, the NF-Y binding sites are located near a Sp1 binding site [4].
Conclusion
Transcription factory NF-Y is significantly downregulated in high doses of retinoic acid. This due to lessened binding potential due to inhibition of CDK mediated phosphorylation of NF-Y.
The effects on C/EBK with high dose RA exposure are unknown. Possible effects on the importins are unknown.
The transcriptional activator NF-Y is a heterotrimeric complex composed of NF-YA, NF-YB, and NF-YC, which specifically binds the CCAAT consensus present in about 30% of eukaryotic promoters. All three subunits contain evolutionarily conserved core regions, which comprise a histone fold motif (HFM) in the case of NF-YB and NF-YC. In vitro binding studies and nuclear import assays reveal two different transport mechanisms for NF-Y subunits. While NF-YA is imported by an importin beta-mediated pathway, the NF-YB/NF-YC heterodimer is translocated into the nucleus in an importin 13-dependent manner. Importin beta binding is restricted to the monomeric, uncomplexed NF-YA subunit. In contrast, the nuclear import of NF-YB and NF-YC requires dimer formation. Only the NF-YB/NF-YC dimer, but not the monomeric components, are recognized by importin 13 and are imported into the nucleus. Importin 13 competes with NF-YA for binding to the NF-YB/NF-YC dimer. Our data suggest that a distinct binding platform derived from the HFM of both subunits, NF-YB/NF-YC, mediates those interactions [1]. C/EBP homologous protein (CHOP) is retinoid-responsive gene [2].
NF-Y transcription through phosphorylation is CDK dependant [3], in a similiar manner to transcription of Sp1 via phosphorylation. Sp1 and NF-Y are ubiquitously expressed. In retinoic acid regulation of several genes, the NF-Y binding sites are located near a Sp1 binding site [4].
Conclusion
Transcription factory NF-Y is significantly downregulated in high doses of retinoic acid. This due to lessened binding potential due to inhibition of CDK mediated phosphorylation of NF-Y.
The effects on C/EBK with high dose RA exposure are unknown. Possible effects on the importins are unknown.