NF-Y-mediatedTrans-activation of the human thymidine kinase promoter is closely linked to activation of cyclin-dependent kinase

Chang, Zee-Fen; Huang, Duen-Yi; Xu, Jianchang

doi:10.1002/(sici)1097-4644(19991101)75:2<300::aid-jcb12>3.0.co;2-z

Cited by 17 publications

(5 citation statements)

References 34 publications

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“…CDK2 has several interactions that impact the transcription of matrix components. CDK2 is an activator of CBF/NF-Y binding [35], [36]. Binding of the CBF/NF-Y to CCAAT boxes activates transcription of multiple procollagen genes (including COL1A1 and COL2A1 ) in response to TGF-β [37], [38], [39].…”

Section: Discussionmentioning

confidence: 99%

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

2012

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Heightened production of collagen and other matrix proteins underlies the fibrotic phenotype of systemic sclerosis (SSc). Roscovitine is an inhibitor of cyclin-dependent kinases that promote cell cycling (CDK1, 2), neuronal development (CDK5) and control transcription (CDK7,9). In an in vivo glomerulonephritis model, roscovitine treatment decreased mesangial cell proliferation and matrix proteins [1]. We investigated whether roscovitine could regulate fibrotic protein production directly rather than through cell cycling. Our investigations revealed that roscovitine coordinately inhibited the expression of collagen, fibronectin, and connective tissue growth factor (CTGF) in normal and SSc fibroblasts. This effect occurred on a transcriptional basis and did not result from roscovitine-mediated cell cycle inhibition. Roscovitine-mediated suppression of matrix proteins could not be reversed by the exogenous profibrotic cytokines TGF-β or IL-6. To our knowledge, we are the first to report that roscovitine modulates matrix protein transcription. Roscovitine may thus be a viable treatment option for SSc and other fibrosing diseases.

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Section: Discussionmentioning

confidence: 99%

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

2012

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“…In general, this is surprising, considering the number of G1/S genes that are functioning through NF-Y, including some of the key regulators of S phase entry (11,18,46,47). The profiling analysis supports the idea that transcription of G1/S genes is less dependent on NF-Y.…”

Section: Discussionmentioning

confidence: 99%

A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response

Benatti

Basile

Merico

et al. 2008

Nucleic Acids Research

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The transcription factor NF-Y is a trimer with histone-like subunits that binds and activates CCAAT-containing promoters. NF-Y controls the expression of several key regulators of the cell cycle. In this study, we examined the functional and molecular effects of NF-YB knockdown. Cell cycle progression is affected with a G2/M-specific depletion. This is due to the inability of activation of G2/M-specific genes, as evidenced by expression profiling, RT-PCR and ChIP data. Surprisingly, apoptosis is also observed, with Caspase 3/7/8 cleavage. A role of p53 and Bcl-2 family members is important. NF-YB inactivation is sufficient to functionally activate p53, in the absence of DNA damage. Failure to maintain a physiologic level of CCAAT-dependent transcription of anti-apoptotic genes contributes to impairment of Bax/Bcl-2 and Bax/Bcl-XL ratios. Our data highlight the importance of fine balancing the NF-Y-p53 duo for cell survival by (i) maintaining transcription of anti-apoptotic genes and (ii) preventing p53 activation that triggers the apoptotic cascade.

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“…Taken together, our data imply complex MAP kinase regulation of the TPH promoter involving perhaps several pathways and interdependent sequence elements including the inverted CCAAT box. NF-Y modulates transcriptional activity through recruitment of other transcription factors, acting as a general promoter organizer rather than a direct transcriptional activator (52)(53)(54)(55)(56). Thus, NF-Y may stabilize the interaction of a cell-specific MAP kinase-responsive protein with the promoter to enhance transcriptional activation.…”

Section: Map Kinase Regulation Requires Multiplementioning

confidence: 99%

Autoregulation of Cell-specific MAP Kinase Control of the Tryptophan Hydroxylase Promoter

Wood

Russo

2001

Journal of Biological Chemistry

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The neurotransmitter serotonin controls a wide range of biological systems, including its own synthesis and release. As the rate-limiting enzyme in serotonin biosynthesis, tryptophan hydroxylase (TPH) is a potential target for this autoregulation. Using the serotonergic neuron-like CA77 cell line, we have demonstrated that treatment with a 5-hydroxytryptamine autoreceptor agonist, CGS 12066A, can lower TPH mRNA levels and promoter activity. We reasoned that this repression might involve inhibition of MAP kinases, since 5-HT1 receptors can increase mitogen-activated protein (MAP) kinase phosphatase levels. To test this hypothesis, we first showed that the TPH promoter can be activated 20-fold by mitogen-activated extracellular-signal regulated kinase kinase kinase (MEKK), an activator of MAP kinases. This activation was then blocked by CGS 12066A. The maximal MAP kinase and CGS repression regulatory region was mapped to between ؊149 and ؊45 base pairs upstream of the transcription start site. The activation by MEKK appears to be cell-specific, because MEKK did not activate the TPH promoter in nonneuronal cell lines. At least part, but not all, of the MAP kinase responsiveness was mapped to an inverted CCAAT box that binds the transcription factor NF-Y. These data suggest a model for the autoregulation of serotonin biosynthesis by repression of MAP kinase stimulation of the TPH promoter. Serotonin (5-hydroxytryptamine; 5-HT)1 is a monoamine neurotransmitter involved in diverse physiological functions including regulation of mood, aggression, anxiety, sleep, satiety, and sexual activity (1). Dysfunction in serotonergic systems has been implicated in the etiology of depression, aggressive behavior, and anxiety disorders (2, 3). The pathophysiological mechanisms behind these illnesses, however, are poorly understood, and very little is known about the control of serotonin levels in neurons.Serotonin biosynthesis is restricted to serotonergic neurons in the brain raphe and gut, the pineal gland, enterochromaffin cells in the gastrointestinal tract, and rodent mast cells (4,5). This is largely due to the cell-specific expression of tryptophan hydroxylase (TPH), the first and rate-limiting step in serotonin biosynthesis, which catalyzes the conversion of tryptophan to 5-hydroxytryptophan. As the rate-limiting enzyme, TPH is a potential target for control of serotonin levels. There is extensive evidence for post-translational regulation of TPH enzyme activity through phosphorylation by Ca 2ϩ /calmodulin-dependent protein kinase, cAMP-dependent protein kinase, and a member of the 14-3-3 protein family (6 -8).Another mechanism for the control of serotonin levels is through a negative feedback loop via activation of presynaptic 5-HT1 autoreceptors, which inhibit neuronal firing and serotonin release (5, 9). Stimulation of 5-HT1 autoreceptors also decreases the conversion of tryptophan to 5-hydroxytryptophan, suggesting that extracellular serotonin can regulate TPH activity (5). No studies to date directly demonstrate that 5...

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NF-Y-mediatedTrans-activation of the human thymidine kinase promoter is closely linked to activation of cyclin-dependent kinase

Cited by 17 publications

References 34 publications

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

Antifibrotic Effects of Roscovitine in Normal and Scleroderma Fibroblasts

A balance between NF-Y and p53 governs the pro- and anti-apoptotic transcriptional response

Autoregulation of Cell-specific MAP Kinase Control of the Tryptophan Hydroxylase Promoter

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