Synonym(s)
HDAC
DefinitionThis section has been translated automatically.
Class of enzymes that induce changes in histone proteins.
General informationThis section has been translated automatically.
- Histones play an important role in the formation of chromatin structures and in the regulation of transcription. Histones represent the protein portion of the chromatin. Acetylation and deacetylation regulate the reading of the genes on the DNA, which lies with its coils on the histones. These processes are controlled by the enzymes histone acetyltransferase and histone deacetylase (HDAC).
- HDAC remove acetyl groups from acetylated lysine to the N-terminal histone end. Through deacetylation, the amino acid lysine regains a positive electrical charge. This increases the affinity of the histone end for the negatively charged phosphate skeleton of the DNA. The subsequent blocking of the DNA for transcription factors downregulates the DNA transcription. This is usually accompanied by the formation of inactive heterochromatin. Inhibition of histone deacetylase results in hyperacetylation of the histones. Among other things, this can cause controlled cell death (apoptosis) of the cancer cells. Normal cells are not affected by histone deacetylase inhibitors to this extent, so that a therapeutic application seems possible in this way.
- Vorinostat is one such histone deacetylase inhibitor and has been approved by the FDA in America for the treatment of cutaneous T-cell lymphoma since October 2006. Initial studies have shown that Vorinostat is well tolerated. In a Phase II study with patients with advanced stage CTCL and described resistance to therapy, it was shown that 30 percent of patients responded to vorinostat.
LiteratureThis section has been translated automatically.
- Grant S et al (2007) Vorinostat. Nat Rev Drug Discov 6: 21-22
- Jenuwein T et al (2001) Translating the histone code. Science 293: 1074-1080
Prof. Dr. med. Peter Altmeyer