Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB

Yamamoto, Karen K.; González, Gustavo; Biggs, William H.; Montminy, Marc

doi:10.1038/334494a0

Cited by 1,292 publications

(698 citation statements)

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“…[16][17][18][19][20][21][22][23] Protein kinases that phosphorylate CREB induce binding of CREB to the CRE consensus sequence in chromatin. These kinases include protein kinase A (PKA), [24][25][26] protein kinase C (PKC), 27 p38 and p44 mitogen-activated protein kinases (MAPK), 28,29 and Ca 2 þ -calmodulin kinase (CaMK) IV. 30 Of relevance to bipolar disorder, BDNF levels are decreased in the serum, 31 and BDNF and phosphorylated CREB levels are decreased in the brain of bipolar patients compared to controls.…”

Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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Decreased docosahexaenoic acid (DHA) and brain-derived neurotrophic factor (BDNF) have been implicated in bipolar disorder. It also has been reported that dietary deprivation of n-3 polyunsaturated fatty acids (PUFAs) for 15 weeks in rats, increased their depression and aggression scores. Here, we show that n-3 PUFA deprivation for 15 weeks decreased the frontal cortex DHA level and reduced frontal cortex BDNF expression, cAMP response element binding protein (CREB) transcription factor activity and p38 mitogen-activated protein kinase (MAPK) activity. Activities of other CREB activating protein kinases were not significantly changed. The addition of DHA to rat primary cortical astrocytes in vitro, induced BDNF protein expression and this was blocked by a p38 MAPK inhibitor. DHA's ability to regulate BDNF via a p38 MAPK-dependent mechanism may contribute to its therapeutic efficacy in brain diseases having disordered cell survival and neuroplasticity.

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Section: Introductionmentioning

confidence: 99%

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

et al. 2006

Mol Psychiatry

258

151

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“…(24) Phosphorylated CREB binds to cyclic AMP response element (CRE) in the promoter region of genes, which regulates gene expression. (25) This represents an integrative set of mechanisms in which antidepressants acting via either NE or 5-HT can target a common set of genes and their respective protein products.…”

Section: Intracellular Signal Transductionmentioning

confidence: 99%

The Molecular Neurobiology of Depression

Shelton

2007

Psychiatric Clinics of North America

130

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The molecular neurobiology of depression begins with an idea: depressive disorders represent a family of related but distinct conditions. Different points of vulnerability in the brain may predispose to depressive disorders. For example, it is likely that the core pathophysiology of depression associated with early life adversity is different from non-trauma related disorders. In particular, the pathophysiology of trauma-related depression involves the hypothalamic-pituitary-adrenal (HPA) axis, although, in turn, this reflects underlying molecular etiologies. In particular, dysregulation of signal transduction mechanisms may be one site of origin. This may be the result of yet other processes such as the effects of reactive oxygen species (ROS) or genomic imprinting. Unraveling these complex causes may lead to novel treatments that can be used in a targeted fashion. Keywords/phrasesDepression; molecular; signal transduction; gene expression; genomics Unipolar depressive disorders encompass a range of features that strongly suggest a neurobiological substrate. These include symptoms such as include sleep and appetite disturbances (both up and down), loss of interest and pleasure, negative rumination, fatigue, and poor concentration, but also apparent abnormalities of the hypothalamic-pituitary-adrenal axis(1) or of neuroplasticity.(2) Moreover, depression appears to have genetic antecedents, which also point to a biological contribution to etiology.(3) However, the exact pathophysiology has been largely unknown until the last decade or so.To begin, depression clearly is not one entity, but subsumes a range of causes that involve genetic contributors, along with early and later stress.(2;4) Therefore, the depressive spectrum include conditions related to early traumatic events (typically with early onset of depression as well), through episodes in the absence of early trauma that may or may not be precipitated by an acute stressor. Therefore, the heterogeneous nature of the condition must be taken into account in any search for a biological substrate.Unfortunately, that is not usually the case. In fact, most studies simply take an unselected groups of "depressed" and "controls" for comparison. However, this is likely to contribute to type II error, since a particular biological finding may be applicable only to a subset of depressed patients. To illustrate this point, take a study from our own research laboratory ( Figure 1).(5) In this study, protein kinase A (PKA) activity was determined in fibroblasts in Mailing address: 1500 21st Avenue, South, Suite 2200, Nashville, TN 37212, Email: richard.shelton@vanderbilt.edu. Supported in part by NIMH grants MH073630, MH01741, and MH52339.Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable fo...

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“…The transcriptional activator CREB was the ®rst member of this class to be described (Hoe er et al, 1988). It has been found that CREB function is tightly regulated by phosphorylation (Yamamoto et al, 1988). Speci®cally, direct phosphorylation by PKA of a serine residue in position 133 converts CREB into a powerful activator (Gonzales and Montminy 1989).…”

Section: Introductionmentioning

confidence: 99%

Cyclic AMP signalling pathway and cellular proliferation: induction of CREM during liver regeneration

et al. 1997

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The CREM gene encodes both activators and repressors of cAMP-induced gene expression. An isoform of CREM encodes the powerful transcriptional repressor ICER (Inducible cAMP Early Repressor), which has been shown to be inducible by virtue of an alternative, intronic promoter. The CREM gene belongs to the early response class and displays a characteristic neuroendocrine cell-and tissue-speci®c expression. To date ICER inducibility has been described in non-replicating, terminally di erentiated tissues. In this paper we document a robust induction of CREM expression in the regenerating rat liver after partial hepatectomy. This represents the ®rst link of inducible CREM expression to the phenomenon of cellular proliferation. Furthermore, it represents the ®rst example of transcriptional activation of a cAMP-responsive factor in the regenerating liver. This has signi®cant physiological relevance since the adenylate cyclase signalling pathway is strongly implicated in liver regeneration. Finally, we show that the repressor ICER is inducible in the hepatoma cell line H35 upon activation of the adenylate cyclase and phosphorylation of the activator CREB.

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Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB

Cited by 1,292 publications

References 16 publications

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

n-3 Polyunsaturated fatty acid deprivation in rats decreases frontal cortex BDNF via a p38 MAPK-dependent mechanism

The Molecular Neurobiology of Depression

Cyclic AMP signalling pathway and cellular proliferation: induction of CREM during liver regeneration

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