The International Journal of Biochemistry & Cell Biology

Leibniz Institute for Age Research - Fritz Lipmann Institute, Beutenbergstrasse 11, 07745 Jena, Germany.
The International Journal of Biochemistry & Cell Biology (Impact Factor: 4.05). 10/2008; 41(1):185-98. DOI: 10.1016/j.biocel.2008.08.027
Source: PubMed


This review focuses on the posttranslational acetylation of non-histone proteins, which determines vital regulatory processes. The recruitment of histone acetyltransferases and histone deacetylases to the transcriptional machinery is a key element in the dynamic regulation of genes controlling cellular proliferation and differentiation. A steadily growing number of identified acetylated non-histone proteins demonstrate that reversible lysine acetylation affects mRNA stability, and the localisation, interaction, degradation and function of proteins. Interestingly, most non-histone proteins targeted by acetylation are relevant for tumourigenesis, cancer cell proliferation and immune functions. Therefore inhibitors of histone deacetylases are considered as candidate drugs for cancer therapy. Histone deacetylase inhibitors alter histone acetylation and chromatin structure, which modulates gene expression, as well as promoting the acetylation of non-histone proteins. Here, we summarise the complex effects of dynamic alterations in the cellular acetylome on physiologically relevant pathways.

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    • " antibodies as described previously ( Nallamilli et al . , 2014 ) . As a result , multiple major protein bands with molecular weight higher than histones were successfully detected ( Figure 2 ) , indicating that lysine acetylation not only happens to histones , but also occurs in non - histone proteins , which is consistent with previous reports ( Spange et al . , 2009 ; Nallamilli et al . , 2014 ) . Lysine acetylomes in plants were previously investigated by a number of researchers . Thus , Smith - Hammond et al . identified 664 acetylation sites in 358 proteins in pea seedling mitochondria ( Smith - Hammond et al . , 2014b ) . Moreover , in Arabidopsis thaliana , Wu et al . identified 64 acetylated "
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    ABSTRACT: Protein lysine acetylation is a reversible and dynamic post-translational modification. It plays an important role in regulating diverse cellular processes including chromatin dynamic, metabolic pathways, and transcription in both prokaryotes and eukaryotes. Although studies of lysine acetylome in plants have been reported, the throughput was not high enough, hindering the deep understanding of lysine acetylation in plant physiology and pathology. In this study, taking advantages of anti-acetyllysine-based enrichment and high-sensitive-mass spectrometer, we applied an integrated proteomic approach to comprehensively investigate lysine acetylome in strawberry. In total, we identified 1392 acetylation sites in 684 proteins, representing the largest dataset of acetylome in plants to date. To reveal the functional impacts of lysine acetylation in strawberry, intensive bioinformatic analysis was performed. The results significantly expanded our current understanding of plant acetylome and demonstrated that lysine acetylation is involved in multiple cellular metabolism and cellular processes. More interestingly, nearly 50% of all acetylated proteins identified in this work were localized in chloroplast and the vital role of lysine acetylation in photosynthesis was also revealed. Taken together, this study not only established the most extensive lysine acetylome in plants to date, but also systematically suggests the significant and unique roles of lysine acetylation in plants.
    Frontiers in Plant Science 09/2015; 6:739. DOI:10.3389/fpls.2015.00739 · 3.95 Impact Factor
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    • "The enzyme family of HDAC contributes to post-translational protein modifications by catalysing the deacetylation of lysine residues in their target proteins [7] [8]. These include not only DNA-associated histones but also a great number of non-histone proteins such as transcription factors and regulators, signal transduction mediators, as well as chaperone and structural proteins [9] [10] [11]. HDAC belonging to class I (HDAC1, 2, 3 and 8), class IIa (HDAC4, 5, 7, 9), and class IIb (HDAC6 and 10) [2] [12] share a zinc(II) cation in the centre of their catalytic cavity, yet differ in their cellular function, (tissue) localisation and protein substrates [2] [10]. "
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    ABSTRACT: Histone deacetylases (HDAC) which play a crucial role in cancer cell proliferation are promising drug targets. However, HDAC inhibitors (HDACi) modelled on natural hydroxamic acids such as trichostatin A frequently lead to resistance or even an increased agressiveness of tumours. As a workaround we developed 4-(1-ethyl-4-anisyl-imidazol-5-yl)-N-hydroxycinnamide (etacrox), a hydroxamic acid that combines HDAC inhibition with synergistic effects of the 4,5-diarylimidazole residue. Etacrox proved highly cytotoxic against a panel of metastatic and resistant cancer cell lines while showing greater specificity for cancer over non-malignant cells when compared to the approved HDACi vorinostat. Like the latter, etacrox and the closely related imidazoles bimacroxam and animacroxam acted as pan-HDACi yet showed some specificity for HDAC6. Akt signalling and interference with nuclear beta-catenin localisation were elicited by etacrox at lower concentrations when compared to vorinostat. Moreover, etacrox disrupted the microtubule and focal adhesion dynamics of cancer cells and inhibited the proteolytic activity of prometastatic and proangiogenic matrix metalloproteinases. As a consequence, etacrox acted strongly antimigratory and antiinvasive against various cancer cell lines in three-dimensional transwell invasion assays and also antiangiogenic in vivo with respect to blood vessel formation in the chorioallantoic membrane assay. These pleiotropic effects and its water-solubility and tolerance by mice render etacrox a promising new HDACi candidate. Copyright © 2015. Published by Elsevier Inc.
    Experimental Cell Research 06/2015; 336(2):263-275. DOI:10.1016/j.yexcr.2015.06.008 · 3.25 Impact Factor
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    • "Acetilación de proteínas no histonas muy próximos, se ha sugerido que puede existir algún tipo de cooperación o interferencia entre estas dos vías de transmisión de señales (Kouzarides, 2000; Spange y col, 2009). "
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    ABSTRACT: Son múltiples los beneficios del ejercicio físico sobre la mente y el cuerpo, y ello es conocido que está en relación con la intensidad y duración del mismo (Cook y Koltyn., 2000). Los cambios notables a nivel mental, dejando de lado la hipótesis de las endorfinas y otros mecanismos implicados (Harbach y col., 2000; Kolata., 2002) carecen de una explicación científica y por tanto, se ha planteado otro mecanismo de acción que induzca estos efectos, siendo postulado el sistema cannabinoide como participante (Gaoni y Mechoulam., 1964; Devane y cols., 1988; Matsuda y col., 1990; Munro y col., 1993) por sus diferentes efectos sobre el cuerpo humano a través no solamente de la activación de receptores específicos (CB1 y CB2), sino también por el aumento de endocannabinoides circulantes. Diversos estudios indican niveles elevados de estos compuestos durante el ejercicio físico (Dietrich y McDaniel., 2004; Keeney y col., 2008; Fuss y Gass., 2010; Garland y col., 2011), lo que puede sugerir la implicación del sistema cannabinoide.
    Sociedad Española de Ciencias Fisiológicas (ISSN: 1889-397X), Spain; 12/2014
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