Regulation of protein turnover by acetyltransferases and deacetylases.
Lysine acetylation was first discovered as a post-translational modification of histones and has long been considered as a direct regulator of chromatin structure and function. Histone acetyltransferases (HATs) and histone deacetylases (HDACs) are the enzymes involved in this modification and they were thought to act as critical gene silencers or activators. Further investigations indicated that lysine acetylation can also occur in non-histone proteins and pointed to HATs and HDACs as multifunctional factors, acting not only on transcription but also on a variety of other cellular processes. One of these processes is the regulation of protein stability. Indeed, at least four independent HATs, namely CBP, p300, PCAF and TAF1, and one HDAC, HDAC6, possess intrinsic ubiquitin-linked functions in addition to their regular HAT/HDAC activities. Furthermore HATs and HDACs can be found in multi-subunit complexes with enzymes of the ubiquitination machinery. Moreover, lysine acetylation itself was found to directly or indirectly affect protein stability. These observations reveal therefore a tight link between protein lysine acetylation and ubiquitination and designate the acetylation machinery as a determinant element in the control of cellular proteolytic activities.
INSERM U823, Equipe Epigénétique et Signalisation Cellulaire, F-38706 Grenoble, France.
Karin
K
Sadoul
Cyril
C
Boyault
Michel
M
Pabion
Saadi
S
Khochbin
D000818:Animals; D051548:Histone Acetyltransferases / Q000737:chemistry / Q000378:metabolism*; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
D011506:Proteins; D025801:Ubiquitin; D051548:Histone Acetyltransferases; D046988:Proteasome Endopeptidase Complex; D006655:Histone Deacetylases; D008239:Lysine