Mammalian Histone Deacetylase 1 Protein Is Posttranslationally Modified by Phosphorylation

Cai, Richard; Kwon, Paul; Yan‐Neale, Yan; Sambuccetti, Lidia; Fischer, Denise; Cohen, Dalia

doi:10.1006/bbrc.2001.4786

Cited by 62 publications

(56 citation statements)

References 45 publications

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“…With the exception of HDAC8, shown to be phosphorylated and thus inactivated by protein kinase A (PKA) [77], casein kinase 2 (CK2) emerged as a key enzyme for all other class I HDAC isotypes [78][79][80][81][82]. CK2 is a multifunctional protein kinase, ubiquitously distributed in both the cytoplasm and the nucleus of eukaryotic cells and most prominently involved in the regulation of cell growth, survival and proliferation [83][84][85], and transcription-related chromatin remodeling [86][87][88].…”

Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

“…These studies raise a number of yet to be reconciled contradictory conclusions, mainly concerning the regulatory effects exerted by phosphorylation on the enzymatic activity, transcriptional repression potential and functional protein-protein interactions [78-81, 91, 92]. Interestingly, HDAC1 and HDAC2 phosphoserine mutations, shown to be deleterious for the enzymatic activity, also disrupt interactions with endogenous associated proteins [78][79][80], including MTA2 and CoREST, essential members of HDAC1/2 enzymatically proficient complexes [63,64]. Phosphorylation might therefore increase the affinity of HDACs for key interacting proteins, which in turn enhance their enzymatic activity.…”

Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

“…Phospho-serine mutagenesis approaches, however, include the caveat that the mutations themselves could alter the HDACs conformation inducing an enzymatically less active form and/or decreasing protein-binding affinity. Published evidence has shown that HDAC1 and HDAC2 immunocomplexes contain functional CK2 [79,81]. More recently, we have identified active CK2 in the HDAC3 immunocomplex capable of efficiently phosphorylating both b-casein and the associated HDAC3 and of autophosphorylating its own regulatory b subunit [91].…”

Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

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HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

et al. 2007

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Histone deacetylases (HDACs) and histone acetyl transferases (HATs) are two counteracting enzyme families whose enzymatic activity controls the acetylation state of protein lysine residues, notably those contained in the N-terminal extensions of the core histones. Acetylation of histones affects gene expression through its influence on chromatin conformation. In addition, several non-histone proteins are regulated in their stability or biological function by the acetylation state of specific lysine residues. HDACs intervene in a multitude of biological processes and are part of a multiprotein family in which each member has its specialized functions. In addition, HDAC activity is tightly controlled through targeted recruitment, protein-protein interactions and post-translational modifications. Control of cell cycle progression, cell survival and differentiation are among the most important roles of these enzymes. Since these processes are affected by malignant transformation, HDAC inhibitors were developed as antineoplastic drugs and are showing encouraging efficacy in cancer patients.

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Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

Section: Ck2 Is a Key Modulator Of Class I Hdac Activitymentioning

confidence: 99%

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HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

et al. 2007

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“…The cAMP signalling pathway has been linked to both SIRT activation and subcellular localization of HDACs (20)(21)(22)(23), and we therefore hypothesized that cAMP antagonizes the IR-mediated acetylation of p53 through HDACs and/or SIRT1. To test this possibility, we examined the effects of the deacetylase inhibitors trichostatin A (TSA) and …”

Section: Camp Inhibits P53 Accumulation and Isoelectric Point Shift Imentioning

confidence: 99%

cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases

Kloster

Naderi

Haaland

et al. 2013

International Journal of Oncology

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Abstract. Activation of cAMP signalling potently inhibits DNA damage-induced apoptosis in acute lymphoblastic leukemia cells by promoting the turnover of p53 protein. Recently, we showed that the cAMP-induced destabilization of p53 in DNA-damaged cells occurs as a result of enhanced interaction between p53 and HDM2. In this report, we present results showing that increased levels of cAMP in cells with DNA damage enhances the deacetylation of p53, an event that facilitates the interaction of p53 with HDM2, thus annulling the stabilizing effect of DNA damage on p53. The combined inhibition of the HDAC and SIRT1 deacetylases abolished the cAMP-mediated deacetylation of p53, implying that cAMP-mediated deacetylation of p53 is dependent on the activity of these two classes of histone deacetylases. Importantly, diminishing the activity of HDACs and SIRT1 was also found to reverse the inhibitory effect of cAMP on the DNA damage-induced p53 stabilization and apoptosis, suggesting the involvement of the p53 acetylation pathway in the anti-apoptotic effect of cAMP signalling.

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“…In the maize embryos, phosphorylation of HD1A causes a change in substrate specificity of the enzyme [52]. Other HDACs, such as the maize HD2 [8], human HDAC1, 2, 4 and 5 [53][54][55] are subjected to phosphorylation, which can modulate their activities. Another post-translational modification that has been shown to regulate HDAC activity and function is called sumoylation, which involves the conjugation of small ubiquitin-related modifier [41,[56][57][58].…”

Section: Recombinant Athd1 Demonstrated Histone Deacetylase Activity mentioning

confidence: 99%

Arabidopsis thaliana histone deacetylase 1 (AtHD1) is localized in euchromatic regions and demonstrates histone deacetylase activity in vitro

2006

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Arabidopsis thaliana histone deacetylase 1 (AtHD1 or AtHDA19), a homolog of yeast RPD3, is a global regulator of many physiological and developmental processes in plants. In spite of the genetic evidence for a role of AtHD1 in plant gene regulation and development, the biochemical and cellular properties of AtHD1 are poorly understood. Here we report cellular localization patterns of AtHD1 in vivo and histone deacetylase activity in vitro. The transient and stable expression of a green fluorescent protein (GFP)-tagged AtHD1 in onion cells and in roots, seeds and leaves of the transgenic Arabidopsis, respectively, revealed that AtHD1 is localized in the nucleus presumably in the euchromatic regions and excluded from the nucleolus. The localization patterns of AtHD1 are different from those of AtHD2 and AtHDA6 that are involved in nucleolus formation and silencing of transgenes and repeated DNA elements, respectively. In addition, a histone deacetylase activity assay showed that the recombinant AtHD1 produced in bacteria demonstrated a specific histone deacetylase activity in vitro. The data suggest that AtHD1 is a nuclear protein and possesses histone deacetylase activities responsible for global transcriptional regulation important to plant growth and development.

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Mammalian Histone Deacetylase 1 Protein Is Posttranslationally Modified by Phosphorylation

Cited by 62 publications

References 45 publications

HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

HDACs, histone deacetylation and gene transcription: from molecular biology to cancer therapeutics

cAMP signalling inhibits p53 acetylation and apoptosis via HDAC and SIRT deacetylases

Arabidopsis thaliana histone deacetylase 1 (AtHD1) is localized in euchromatic regions and demonstrates histone deacetylase activity in vitro

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