Phosphorylation of Conserved Casein Kinase Sites Regulates cAMP-response Element-binding Protein DNA Binding in Drosophila

Horiuchi, Junjiro; Jiang, Wei; Zhou, Hong; Wu, Priscilla; Yin, Jie

doi:10.1074/jbc.m212839200

Cited by 28 publications

(36 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In Drosophila, it has been shown that the KID domain of most dCREB2 proteins exists in a phosphorylated active state. As a result, in Drosophila, CREB activity has been postulated to be controlled at the level of DNA binding to its DNA elements [55]. Two putative CRE sites were identified close to 55b in the slo control region by sequence analysis.…”

Section: Resultsmentioning

confidence: 99%

Drug-Induced Epigenetic Changes Produce Drug Tolerance

et al. 2007

View full text Add to dashboard Cite

Tolerance to drugs that affect neural activity is mediated, in part, by adaptive mechanisms that attempt to restore normal neural excitability. Changes in the expression of ion channel genes are thought to play an important role in these neural adaptations. The slo gene encodes the pore-forming subunit of BK-type Ca2+-activated K+ channels, which regulate many aspects of neural activity. Given that induction of slo gene expression plays an important role in the acquisition of tolerance to sedating drugs, we investigated the molecular mechanism of gene induction. Using chromatin immunoprecipitation followed by real-time PCR, we show that a single brief sedation with the anesthetic benzyl alcohol generates a spatiotemporal pattern of histone H4 acetylation across the slo promoter region. Inducing histone acetylation with a histone deacetylase inhibitor yields a similar pattern of changes in histone acetylation, up-regulates slo expression, and phenocopies tolerance in a slo-dependent manner. The cAMP response element binding protein (CREB) is an important transcription factor mediating experience-based neuroadaptations. The slo promoter region contains putative binding sites for the CREB transcription factor. Chromatin immunoprecipitation assays show that benzyl alcohol sedation enhances CREB binding within the slo promoter region. Furthermore, activation of a CREB dominant-negative transgene blocks benzyl alcohol–induced changes in histone acetylation within the slo promoter region, slo induction, and behavioral tolerance caused by benzyl alcohol sedation. These findings provide unique evidence that links molecular epigenetic histone modifications and transcriptional induction of an ion channel gene with a single behavioral event.

show abstract

Section: Resultsmentioning

confidence: 99%

Drug-Induced Epigenetic Changes Produce Drug Tolerance

et al. 2007

View full text Add to dashboard Cite

show abstract

“…This could be due to differences in the regulatory mechanisms controlling mammalian and fly CREBs. In contrast to mammalian CREB whose activity is mostly correlated with the phosphorylation level of Ser-133, a large portion of dCREB2 exists with Ser-231 in a phosphorylated state, suggesting that other mechanisms must be important in regulating its activity (38). Alternatively, polyQ in this fly model is overexpressed as a peptide, whereas other studies have used polyQ runs in the context of htt protein residues surrounding the expansion.…”

Section: Discussionmentioning

confidence: 99%

“…Anti-dCREB2 monoclonal and Ser-231 phosphospecific anti-pCREB rabbit polyclonal antibodies have been described (38).…”

mentioning

confidence: 99%

cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity inDrosophila

Iijima-Ando

Drier

et al. 2005

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

Self Cite

View full text Add to dashboard Cite

Gene-specific expansion of polyglutamine-encoding CAG repeats can cause neurodegenerative disorders, including Huntington's disease. It is believed that part of the pathological effect of the expanded protein is due to transcriptional dysregulation. Using Drosophila as a model, we show that cAMP-response elementbinding protein (CREB) is involved in expanded polyglutamineinduced toxicity. A mutation in the Drosophila homolog of CREB, dCREB2, enhances lethality due to polyglutamine peptides (polyQ), and an additional copy of dCREB2 partially rescues this lethality. Neuronal expression of expanded polyQ attenuates in vivo CREmediated transcription of a reporter gene. As reported previously, overexpression of heat-shock protein 70 (Hsp70) rescues polyglutamine-dependent lethality. However, it does not rescue CREBmediated transcription. The protective effects of CREB and heatshock protein 70 against polyQ are additive, suggesting that targeting multiple pathways may be effective for treatment of polyglutamine diseases.transcription ͉ polyglutamine diseases ͉ molecular chaperones ͉ PKA E xpansion of polyglutamine-encoding repeats is implicated in the etiology of at least nine neurological disorders (for review, see ref. 1). It is known that long polyglutamine peptides (polyQ) themselves are sufficient to induce neurodegeneration (2), suggesting that the naturally occurring expansions cause disease due to a gain-of-function mechanism. There is evidence that polyQ expansion targets multiple cellular functions, including transcription, proteasomal degradation, molecular chaperones, and axonal transport (for review, see ref.3).For some of these diseases, aspects of the pathology are attributable to transcriptional dysregulation. Proteins with expanded polyglutamine stretches can interact with transcriptional cofactors, and transcription is altered in mouse models or patients with polyglutamine expansions (for review, see ref. 4). Transcription cofactors, including cAMP-response element-binding protein-(CREB) binding protein (CBP) and TAFII130, have been found in inclusions in cell culture models or patients of polyglutamine diseases (5-8), and sequestration of these proteins into insoluble aggregates has been suspected to contribute to transcriptional dysregulation. It has been reported that polyQ can inhibit the acetyltransferase activity of CBP (9). Accordingly, inhibition of histone deacetylase activity (9, 10), or overexpression of CBP (8, 11), can reverse the deleterious effects due to expanded polyQ proteins.CREB is one of the transcription factors that interact with CBP, and it has been implicated in the pathology of polyglutamine diseases. CREB-mediated transcription of reporter genes is attenuated in cultured cells that transiently express polyQ (5-8, 12, 13). Many genes regulated by the cAMP signaling pathway are down-regulated at an early symptomatic stage in cellular and mouse models of Huntington's disease (12,14). Forskolin stimulation of adenylyl cyclase, as well as overexpression of an activated CREB, amel...

show abstract

“…This might also apply to honeybee lLTM formation, which depends on the bees' feeding state (Friedrich et al 2004). Third, research in the fruit fly suggests that the rate limiting step for the D. melanogaster dCREB2 activity is not the phosphorylation of the S133 homologous serine residue but the nuclear entry and DNA binding of dCREB2, which is regulated by phosphorylation of residues other than the S133 homologous one (Horiuchi et al 2004). Moreover, the nuclear entry rate of pCREB2 correlates with memory formation (Fropf et al 2013).…”

Section: The Level Of Pamcreb Is Not Altered Directly After Classicalmentioning

confidence: 99%

Involvement of phosphorylated Apis mellifera CREB in gating a honeybee's behavioral response to an external stimulus

et al. 2016

View full text Add to dashboard Cite

The transcription factor cAMP-response element-binding protein (CREB) is involved in neuronal plasticity. Phosphorylation activates CREB and an increased level of phosphorylated CREB is regarded as an indicator of CREB-dependent transcriptional activation. In honeybees (Apis mellifera) we recently demonstrated a particular high abundance of the phosphorylated honeybee CREB homolog (pAmCREB) in the central brain and in a subpopulation of mushroom body neurons. We hypothesize that these high pAmCREB levels are related to learning and memory formation. Here, we tested this hypothesis by analyzing brain pAmCREB levels in classically conditioned bees and bees experiencing unpaired presentations of conditioned stimulus (CS) and unconditioned stimulus (US). We demonstrate that both behavioral protocols display differences in memory formation but do not alter the level of pAmCREB in bee brains directly after training. Nevertheless, we report that bees responding to the CS during unpaired stimulus presentations exhibit higher levels of pAmCREB than nonresponding bees. In addition, Trichostatin A, a histone deacetylase inhibitor that is thought to enhance histone acetylation by CREB-binding protein, increases the bees' CS responsiveness. We conclude that pAmCREB is involved in gating a bee's behavioral response driven by an external stimulus.

show abstract

Phosphorylation of Conserved Casein Kinase Sites Regulates cAMP-response Element-binding Protein DNA Binding in Drosophila

Cited by 28 publications

References 38 publications

Drug-Induced Epigenetic Changes Produce Drug Tolerance

Drug-Induced Epigenetic Changes Produce Drug Tolerance

cAMP-response element-binding protein and heat-shock protein 70 additively suppress polyglutamine-mediated toxicity inDrosophila

Involvement of phosphorylated Apis mellifera CREB in gating a honeybee's behavioral response to an external stimulus

Contact Info

Product

Resources

About