Acetylation of non-histone proteins modulates cellular signalling at multiple levels

Spange, Stephanie; Wagner, Tobias; Heinzel, Thorsten; Krämer, Oliver H.

doi:10.1016/j.biocel.2008.08.027

Cited by 601 publications

(533 citation statements)

References 224 publications

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“…2C Right). Although it will require further investigations to determine the role of this specific PTM on c-Src, it may be conceivable that N ε -lysine acetylation could affect c-Src turnover or function (25), influencing Cx43 phosphorylation in mdx. Intriguingly, c-Abl, another c-Src family member, has been previously reported as acetylated on lysine, with important consequences on its intracellular localization and function (26).…”

Section: Resultsmentioning

confidence: 99%

N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

Colussi

Rosati

Straino

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

107

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Wanting to explore the epigenetic basis of Duchenne cardiomyopathy, we found that global histone acetylase activity was abnormally elevated and the acetylase P300/CBP-associated factor (PCAF) coimmunoprecipitated with connexin 43 (Cx43), which was N ε -lysine acetylated and lateralized in mdx heart. This observation was paralleled by Cx43 dissociation from N-cadherin and zonula occludens 1, whereas pp60-c-Src association was unaltered. In vivo treatment of mdx with the pan-histone acetylase inhibitor anacardic acid significantly reduced Cx43 N ε -lysine acetylation and restored its association to GAP junctions (GJs) at intercalated discs. Noteworthy, in normal as well as mdx mice, the class IIa histone deacetylases 4 and 5 constitutively colocalized with Cx43 either at GJs or in the lateralized compartments. The class I histone deacetylase 3 was also part of the complex. Treatment of normal controls with the histone deacetylase pan-inhibitor suberoylanilide hydroxamic acid (MC1568) or the class IIa-selective inhibitor 3-{4-[3-(3-fluorophenyl)-3-oxo-1-propen-1-yl]-1-methyl-1H-pyrrol-2-yl}-N-hydroxy-2-propenamide (MC1568) determined Cx43 hyperacetylation, dissociation from GJs, and distribution along the long axis of ventricular cardiomyocytes. Consistently, the histone acetylase activator pentadecylidenemalonate 1b (SPV106) hyperacetylated cardiac proteins, including Cx43, which assumed a lateralized position that partly reproduced the dystrophic phenotype. In the presence of suberoylanilide hydroxamic acid, cell to cell permeability was significantly diminished, which is in agreement with a Cx43 close conformation in the consequence of hyperacetylation. Additional experiments, performed with Cx43 acetylation mutants, revealed, for the acetylated form of the molecule, a significant reduction in plasma membrane localization and a tendency to nuclear accumulation. These results suggest that Cx43 N ε -lysine acetylation may have physiopathological consequences for cell to cell coupling and cardiac function. muscular dystrophy | protein acetylation

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Section: Resultsmentioning

confidence: 99%

N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

Colussi

Rosati

Straino

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

107

View full text Add to dashboard Cite

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“…This view is supported by a number of recent studies exploring changes in histone phosphorylation and acetylation at the promoters of Per1, c-fos, fosB, bdnf, and NK1R, among other genes, in response to the acute administration of HDACi or drugs of abuse (Kumar et al, 2005;Levine et al, 2005;Renthal et al, 2008aRenthal et al, , 2009Renthal et al, , 2007Russo et al, 2009;Schroeder et al, 2008). However, it should be also noted that HDACs deacetylate not only nucleosome histones, but also a much wider range of cellular proteins and can, therefore, also influence cell physiology and animal behavior through nongenomic mechanisms (Glozak et al, 2005;Spange et al, 2009). Indeed, some behavioral consequences observed after the administration of HDACi might be difficult to reconcile with the temporal requirements of the genomic actions of these compounds, which imply not only gene transcription but also the synthesis of proteins de novo and their transport to cellular structures/organelles.…”

Section: Discussionmentioning

confidence: 97%

Selective Boosting of Transcriptional and Behavioral Responses to Drugs of Abuse by Histone Deacetylase Inhibition

Sanchis‐Segura

López‐Atalaya

Barco

2009

Neuropsychopharmacol

122

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Histone acetylation and other modifications of the chromatin are important regulators of gene expression and, consequently, may contribute to drug-induced behaviors and neuroplasticity. Earlier studies have shown that a reduction in histone deacetylase (HDAC) activity results in the enhancement of some psychostimulant-induced behaviors. In this study, we extend those seminal findings by showing that the administration of the HDAC inhibitor sodium butyrate enhances morphine-induced locomotor sensitization and conditioned place preference. In contrast, this compound has no effects on the development of morphine tolerance and dependence. Similar effects were observed for cocaine and ethanol-induced behaviors. These behavioral changes were accompanied by a selective boosting of a component of the transcriptional program activated by chronic morphine administration that included circadian clock genes and other genes relevant to addictive behavior. Our results support a specific function for histone acetylation and the epigenetic modulation of transcription at a reduced number of biologically relevant loci on non-homeostatic, long-lasting, drug-induced behavioral plasticity.

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“…Studies in different species reveal convincing evidence for a fundamental role of post-translational protein acetylation in basic cellular processes by regulating stability, localization, interaction, and activity of proteins (Choudhary et al 2009;Spange et al 2009;Yuan and Marmorstein 2013). Members of the HAT family p300/ CBP sensitive to C646 are known for their role in transcriptional regulation and histone modification.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

et al. 2016

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Acetylation of histones changes the efficiency of the transcription processes and thus contributes to the formation of longterm memory (LTM). In our comparative study, we used two inhibitors to characterize the contribution of different histone acetyl transferases (HATs) to appetitive associative learning in the honeybee. For one we applied garcinol, an inhibitor of the HATs of the p300 (EP300 binding protein)/CBP (CREB-binding protein) family, and the HATs of the PCAF (p300/ CBP-associated factor) family. As comparative agent we applied C646, a specific inhibitor that selectively blocks HATS of the p300/CBP family. Immunochemical analysis reveals differences in histone H3 acetylation in the honeybee brain, in response to the injection of either C646 or garcinol. Behavioral assessment reveals that the two drugs cause memory impairment of different nature when injected after associative conditioning: processes disturbed by garcinol are annihilated by the established transcription blocker actinomycin D and thus seem to require transcription processes. Actions of C646 are unaltered by actinomycin D, and thus seem to be independent of transcription. The outcome of our different approaches as summarized suggests that distinct HATs contribute to different acetylation-mediated processes in memory formation. We further deduce that the acetylation-mediated processes in memory formation comprise transcription-dependent and transcription-independent mechanisms.

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Acetylation of non-histone proteins modulates cellular signalling at multiple levels

Cited by 601 publications

References 224 publications

N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

Selective Boosting of Transcriptional and Behavioral Responses to Drugs of Abuse by Histone Deacetylase Inhibition

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

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Acetylation of non-histone proteins modulates cellular signalling at multiple levels

Cited by 601 publications

References 224 publications

N ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

N ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

Selective Boosting of Transcriptional and Behavioral Responses to Drugs of Abuse by Histone Deacetylase Inhibition

Inhibition of different histone acetyltransferases (HATs) uncovers transcription-dependent and -independent acetylation-mediated mechanisms in memory formation

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N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart

N ^ε -lysine acetylation determines dissociation from GAP junctions and lateralization of connexin 43 in normal and dystrophic heart