14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila

Karam, Caline S.; Kellner, Wendy A.; Takenaka, Naomi; Clemmons, Alexa W.; Corcés, Victor G.

doi:10.1371/journal.pgen.1000975

Cited by 54 publications

(56 citation statements)

References 49 publications

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“…Members of the evolutionary conserved 14-3-3 family of proteins have previously been implicated in the regulation of various signalling pathways for cell survival, proliferation and development (Acevedo et al, 2007;Benton et al, 2002;Broadie et al, 1997;Chen et al, 2003;Darling et al, 2005;Grammenoudi et al, 2008;Guthridge et al, 2004;Guthridge et al, 2006;Karam et al, 2010;Li et al, 1997;Skoulakis and Davis, 1996;Skoulakis and Davis, 1998;Su et al, 2001;Thomas et al, 2005). However, the specific action of these proteins has been difficult to define, mainly because of the functional redundancy between 14-3-3 homologues in vertebrates.…”

Section: Discussionmentioning

confidence: 99%

Drosophila14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity

Shandala

Woodcock

et al. 2011

Journal of Cell Science

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The secretion of anti-microbial peptides is recognised as an essential step in innate immunity, but there is limited knowledge of the molecular mechanism controlling the release of these effectors from immune response cells. Here, we report that Drosophila 14-3-3ε mutants exhibit reduced survival when infected with either Gram-positive or Gram-negative bacteria, indicating a functional role for 14-3-3ε in innate immunity. In 14-3-3ε mutants, there was a reduced release of the anti-microbial peptide Drosomycin into the haemolymph, which correlated with an accumulation of Drosomycin-containing vesicles near the plasma membrane of cells isolated from immune response tissues. Drosomycin appeared to be delivered towards the plasma membrane in Rab4- and Rab11-positive vesicles and smaller Rab11-positive vesicles. RNAi silencing of Rab11 and Rab4 significantly blocked the anterograde delivery of Drosomycin from the perinuclear region to the plasma membrane. However, in 14-3-3ε mutants there was an accumulation of small Rab11-positive vesicles near the plasma membrane. This vesicular phenotype was similar to that observed in response to the depletion of the vesicular Syntaxin protein Syx1a. In wild-type Drosophila immune tissue, 14-3-3ε was detected adjacent to Rab11, and partially overlapping with Syx1a, on vesicles near the plasma membrane. We conclude that 14-3-3ε is required for Rab11-positive vesicle function, which in turn enables antimicrobial peptide secretion during an innate immune response.

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Section: Discussionmentioning

confidence: 99%

Drosophila14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity

Shandala

Woodcock

et al. 2011

Journal of Cell Science

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“…This modification is recognized by the 14-3-3ζ protein, a member of the 14-3-3 protein family [76]. Furthermore, studies in Drosophila melanogaster have indicated that this protein family is involved in recruiting components of the elongation complex to chromatin [77]. Another example of a protein that specifically binds to phosphorylated histones is MDC1, which is involved in the DNArepair process and is recruited to sites of double-strand DNA breaks (DSB).…”

Section: Regulating the Binding Of Chromatin Factorsmentioning

confidence: 99%

Regulation of chromatin by histone modifications

2011

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Chromatin is not an inert structure, but rather an instructive DNA scaffold that can respond to external cues to regulate the many uses of DNA. A principle component of chromatin that plays a key role in this regulation is the modification of histones. There is an ever-growing list of these modifications and the complexity of their action is only just beginning to be understood. However, it is clear that histone modifications play fundamental roles in most biological processes that are involved in the manipulation and expression of DNA. Here, we describe the known histone modifications, define where they are found genomically and discuss some of their functional consequences, concentrating mostly on transcription where the majority of characterisation has taken place.

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“…In mammalian cells, 14-3-3 was shown to recruit the H4K16 acetyltransferase males absent on the first (MOF), resulting in acetylation-dependent recruitment of the elongation factor P-TEFb via the bromodomain protein BRD4 (73). In Drosophila, 14-3-3 recruits the acetyltransferase Elongator protein 3, which acetylates histone H3 at Lys-9 (74).…”

Section: Map Kinase Activation Sensitizes Resting Cells To Hdacmentioning

confidence: 99%

A Phosphorylation Switch Regulates the Transcriptional Activation of Cell Cycle Regulator p21 by Histone Deacetylase Inhibitors

Simboeck

Sawicka

Zupkovitz

et al. 2010

Journal of Biological Chemistry

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Histone deacetylase inhibitors induce cell cycle arrest and apoptosis in tumor cells and are, therefore, promising anticancer drugs. The cyclin-dependent kinase inhibitor p21 is activated in histone deacetylase (HDAC) inhibitor-treated tumor cells, and its growth-inhibitory function contributes to the anti-tumorigenic effect of HDAC inhibitors. We show here that induction of p21 by trichostatin A involves MAP kinase signaling. Activation of the MAP kinase signaling pathway by growth factors or stress signals results in histone H3 serine 10 phosphorylation at the p21 promoter and is crucial for acetylation of the neighboring lysine 14 and recruitment of activated RNA polymerase II in response to trichostatin A treatment. In non-induced cells, the protein phosphatase PP2A is associated with the p21 gene and counteracts its activation. Induction of p21 is linked to simultaneous acetylation and phosphorylation of histone H3. The dual modification mark H3S10phK14ac at the activated p21 promoter is recognized by the phospho-binding protein 14-3-3, which protects the phosphoacetylation mark from being processed by PP2A. Taken together we have revealed a cross-talk of reversible phosphorylation and acetylation signals that controls the activation of p21 by HDAC inhibitors and identify the phosphatase PP2A as chromatin-associated transcriptional repressor in mammalian cells.Post-translational modifications of histones, such as acetylation, methylation, phosphorylation, and sumoylation play important roles in the regulation of chromatin accessibility and gene expression. The transformation of a differentiated resting cell into a highly proliferative tumor cell is accompanied by a severe change of the gene expression profile, which in turn is the direct consequence of acquired/accumulated tumor suppressor and oncogene mutations. In addition to these genetic alterations, epigenetic alterations are also involved in the development of cancer. These include covalent post-translational modifications of histones and changes in the methylation status of cytosines within CpG islands (1, 2). Therefore, compounds that target these epigenetic changes are of potential interest for anti-tumor therapies. Indeed, histone deacetylase (HDAC) 5 inhibitors have been shown to induce cell cycle arrest, differentiation, or apoptosis in tumor cells and are, therefore, promising anti-tumor drugs (3-5).One of the genes that is activated by different HDAC inhibitors encodes the cyclin-dependent kinase (CDK) inhibitor p21 cip1/waf1 (referred to as p21 thereafter) (3, 4). The p21 protein is a member of the CIP/KIP family of cyclin-dependent kinase inhibitors consisting of p21, p27, and p57. The different members of the CIP/KIP family share a conserved region at the N terminus that is required and sufficient for the inhibition of cyclin-Cdk complexes (6, 7). The p21 protein preferentially inactivates cyclin E/Cdk2 complexes, thereby blocking the inactivating phosphorylation of pRb, which represses genes important for S phase entry. In addition, p21 ...

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14-3-3 Mediates Histone Cross-Talk during Transcription Elongation in Drosophila

Cited by 54 publications

References 49 publications

Drosophila14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity

Drosophila14-3-3ε has a crucial role in anti-microbial peptide secretion and innate immunity

Regulation of chromatin by histone modifications

A Phosphorylation Switch Regulates the Transcriptional Activation of Cell Cycle Regulator p21 by Histone Deacetylase Inhibitors

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