News Update on Deacetylase Research: Sep – 2019

hSIR2SIRT1 Functions as an NAD-Dependent p53 Deacetylase

DNA damage-induced acylation of p53 macromolecule results in its activation and either growth arrest or necrobiosis. we tend to show here that the macromolecule product of the sequence hSIR2SIRT1, the human homolog of the S. cerevisiae Sir2 macromolecule illustrious to be concerned in cell aging and within the response to DNA injury, binds and deacetylates the p53 macromolecule with a specificity for its C-terminal Lys382 residue, modification of that has been concerned within the activation of p53 as a transcription issue. Expression of wild-type hSir2 in human cells reduces the transcriptional activity of p53. In distinction, expression of a catalytically inactive hSir2 macromolecule potentiates p53-dependent necrobiosis and sensitiveness. [1]

Stress-Dependent Regulation of FOXO Transcription Factors by the SIRT1 Deacetylase

The Sir2 deacetylase modulates organismic life-span in numerous species. However, the molecular mechanisms by that Sir2 will increase longevity area unit mostly unknown. we have a tendency to show that in class cells, the Sir2 homolog SIRT1 seems to manage the cellular response to worry by regulation the FOXO family of Forkhead transcription factors, a family of proteins that operate as sensors of the hypoglycemic agent sign pathway and as regulators of organismic longevity. SIRT1 and also the FOXO transcription issue FOXO3 shaped a posh in cells in response to aerophilous stress, and SIRT1 deacetylated FOXO3 in vitro and at intervals cells. SIRT1 had a twin impact on FOXO3 function: SIRT1 multiplied FOXO3’s ability to induce cell cycle arrest and resistance to aerophilous stress however repressed FOXO3’s ability to induce necrobiosis. [2]

The Human Histone Deacetylase Family

Since the identification of the primary simple protein deacetylase (Taunton et al., Science 272, 408–411), many new members are isolated. they’ll loosely be separated into entities on the idea of their similarity to numerous yeast simple protein deacetylases. the primary category is delineated  by its closeness to the yeast Rpd3-like proteins, and also the second last discovered category is similar to yeast Hda1-like proteins. However, because of the very fact that many totally different analysis teams isolated the Hda1-like simple protein deacetylases severally, there are various totally different nomenclatures wont to describe the assorted members, which might cause confusion within the interpretation of this family’s functions and interactions. [3]

Retinoblastoma protein recruits histone deacetylase to repress transcription

The malignant tumor macromolecule (Rb) silences specific genes that area unit active within the S part of the cell cycle and that area unit regulated by E2F transcription factors1. atomic number 37 binds to the activation domain of E2F so actively represses the promoter by a mechanism that’s poorly understood2,3. Here we have a tendency to show that atomic number 37 associates with a simple protein deacetylase, HDAC1, through the atomic number 37 ‘pocket’ domain. Association with the deacetylase is reduced by present mutations within the pocket and by binding of the human benign tumor virus oncoprotein E7. [4]

Prediction of the Inhibitory Concentration of Hydroxamic Acids by DFT-QSAR Models on Histone Deacetylase 1

In order to review the connection between repressive concentration and also the molecular structures of hydroxamic acids, a Quantitative Structure Activity Relationship (QSAR) study is applied to a group of thirty one simple protein deacetylase inhibitors (HDACi). This study is performed by exploitation the Principal element Analysis (PCA) technique, the Ascendant stratified Classification (AHC), the Linear multivariate analysis technique (RML) and also the nonlinear regression (RMNL). variable applied mathematics analysis allowed to get 2 quantitative models (RML model and RMNL model) by the suggests that of the quantum descriptors those are the moment (μ), the bond length d(C=O) and also the valence angles α°(O=C-N) and α°(H-N-O). [5]


[1] Vaziri, H., Dessain, S.K., Eaton, E.N., Imai, S.I., Frye, R.A., Pandita, T.K., Guarente, L. and Weinberg, R.A., 2001. hSIR2SIRT1 functions as an NAD-dependent p53 deacetylase. Cell, 107(2), pp.149-159. (Web Link)

[2] Brunet, A., Sweeney, L.B., Sturgill, J.F., Chua, K.F., Greer, P.L., Lin, Y., Tran, H., Ross, S.E., Mostoslavsky, R., Cohen, H.Y. and Hu, L.S., 2004. Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase. science, 303(5666), pp.2011-2015. (Web Link)

[3] Gray, S.G. and Ekström, T.J., 2001. The human histone deacetylase family. Experimental cell research, 262(2), pp.75-83. (Web Link)

[4] Retinoblastoma protein recruits histone deacetylase to repress transcription
Alexander Brehm, Eric A. Miska, Dennis J. McCance, Juliet L. Reid, Andrew J. Bannister & Tony Kouzarides
Naturevolume 391, pages597–601 (1998) (Web Link)

[5] Soro, D., Ekou, L., Guy-Richard Koné, M., Ekou, T., Thomas Affi, S., Ouattara, L. and Ziao, N. (2018) “Prediction of the Inhibitory Concentration of Hydroxamic Acids by DFT-QSAR Models on Histone Deacetylase 1”, International Research Journal of Pure and Applied Chemistry, 16(2), pp. 1-13. doi: 10.9734/IRJPAC/2018/40895. (Web Link)

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