Deacetylase Enzymes
2002; Elsevier BV; Volume: 9; Issue: 1 Linguagem: Inglês
10.1016/s1074-5521(02)00092-3
ISSN1879-1301
AutoresChristina M. Grozinger, Stuart L. Schreiber,
Tópico(s)Autophagy in Disease and Therapy
ResumoThe reversible acetylation of histones plays a critical role in transcriptional regulation in eukaryotic cells, and there is mounting evidence that acetylation of non-histone substrates is important for other cellular processes (reviewed in [1]). Two families of deacetylase enzymes have been identified: the histone deacetylases, or HDACs, and the Sir2 (silent information regulator)-like family of NAD-dependent deacetylases, or sirtuins (reviewed in [2]). Both families have been evolutionarily conserved from prokaryotes to humans, and both consist of several different proteins with nonredundant cellular functions, many of which involve transcriptional regulation. Several processes have evolved to control the activity of deacetylases; such processes range from the recruitment of these proteins by specific transcription factors to the more general inactivation of the deacetylases by sequestration. In the case of HDACs, small-molecule inhibitors have proven to be crucial for the identification and subsequent characterization of these enzymes. Structural differences among the members of this family suggest that it will be possible to develop specific inhibitors for each of these proteins, which would be useful for elucidating their individual cellular functions. In the case of the sirtuins, no functional characterization of any of the human proteins has been reported. Thus, the recent identification of a sirtuin deacetylase inhibitor [3] may provide a very powerful tool for studying the biology of these enzymes.
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