Overexpression of protein kinase G using adenovirus inhibits cyclin E transcription and mesangial cell cycle

Hanada, Satoko; Terada, Yoshio; Inoshita, Seiji; Sasaki, Sei; Lohmann, Suzanne M.; Smolenski, Albert; Marumo, Fumiaki

doi:10.1152/ajprenal.2001.280.5.f851

Cited by 16 publications

(14 citation statements)

References 35 publications

(33 reference statements)

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“…Our data on neuroblastomas suggest a major role for the cGMP pathway in mediating the interaction between NO and Rb, because both a NO donor and a c-GMP analog replicated the inhibition of Rb phosphorylation in parental cells. A similar picture of the interactions between the cGMP system and Rb has recently emerged from a study in a different cellular model (Hanada et al, 2001). …”

Section: No Negatively Regulates N-myc Expressionmentioning

confidence: 62%

Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Ciani

Severi

Contestabile

et al. 2004

Journal of Cell Science

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Nitric oxide (NO) has been found to act as an important negative regulator of cell proliferation in several systems. We report here that NO negatively regulates proliferation of neuronal cell precursors and promotes their differentiation by downregulating the oncogene N-Myc. We have studied this regulatory function of NO in neuroblastoma cell lines (SK-N-BE) and in primary cerebellar granule cell cultures. In a neuronal NO synthase (nNOS) overexpressing neuroblastoma cell line exposed to the differentiative action of retinoic acid, NO slowed down proliferation and accelerated differentiation towards a neuronal phenotype. This effect was accompanied by a parallel decrease of N-Myc expression. Similar results could be obtained in parental SK-N-BE cells by providing an exogenous source of NO. Pharmacological controls demonstrated that NO's regulatory actions on cell proliferation and N-Myc expression were mediated by cGMP as an intermediate messenger. Furthermore, NO was found to modulate the transcriptional activity of N-Myc gene promoter by acting on the E2F regulatory region, possibly through the control of Rb phosphorylation state, that we found to be negatively regulated by NO. In cerebellar granule cell cultures, NOS inhibition increased the division rate of neuronal precursors, in parallel with augmented N-Myc expression. Because a high N-Myc expression level is essential for neuroblastoma progression as well as for proliferation of neuronal precursors, its negative regulation by NO highlights a novel physiopathological function of this important messenger molecule.

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Section: No Negatively Regulates N-myc Expressionmentioning

confidence: 62%

Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Ciani

Severi

Contestabile

et al. 2004

Journal of Cell Science

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“…Both isoforms of cGK I α and β were demonstrated to be present in cardiac fibroblasts and could potentially participate in antiproliferative action. Antiproliferative effects of cGK I have been described for the β isoform of cGK I in smooth muscle [36], BHK cells [37], mesangial cells [38] and T cells [39]. Recently cGMP and cAMP effects on PDGF-BB-induced proliferation were studied in rat cardiac fibroblasts [40].…”

Section: Discussionmentioning

confidence: 99%

“…For proliferation assays, mouse cardiac fibroblasts (passage 15-20 as well as passage [27][28][29][30][31][32][33][34][35][36][37][38][39] were seeded onto 12 well plates (Greiner, Frickenhausen, Germany) at a density of 500 cells/cm 2 . Subconfluent cells were starved in medium containing 0.1 % FCS for 2 days, then cell proliferation was stimulated for 48 h by the addition of fresh medium containing 5 % FCS in the presence or absence of 8-pCPT-cGMP (Biolog, Bremen, Germany).…”

Section: Cell Proliferation Assaymentioning

confidence: 99%

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

et al. 2004

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SummaryCardiac fibroblasts regulate tissue repair and remodeling in the heart. To quantify transcript levels in these cells we performed a comprehensive gene expression study using serial analysis of gene expression (SAGE). Among 110,169 sequenced tags we could identify 30,507 unique transcripts. A comparison of SAGE data from cardiac fibroblasts with data derived from total mouse heart revealed a number of fibroblast-specific genes. Cardiac fibroblasts expressed a specific collection of collagens, matrix proteins and metalloproteinases, growth factors, and components of signalling pathways. The NO/cGMP signalling pathway was represented by the mRNAs for α 1 and β 1 subunits of guanylyl cyclase, cGMP-dependent protein kinase type I (cGK I) and interestingly the G-kinase anchoring protein GKAP42. The expression of cGK I was verified by RT-PCR and Western Blot. To establish a functional role for cGK I in cardiac fibroblasts we studied its effect on cell proliferation. Selective activation of cGK I with a cGMP-analog inhibited the proliferation of serum-stimulated cardiac fibroblasts which express cGK I, but not higher passage fibroblasts which contain no detectable cGK I. Currently, our data suggest that cGK I mediates the inhibitory effects of the NO/cGMP pathway on cardiac fibroblast growth.Furthermore the SAGE library of transcripts expressed in cardiac fibroblasts provides a basis for future investigations into the pathological regulatory mechanisms underlying cardiac fibrosis.

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“…Both cGMP and over expression of its downstream kinase, cGMP-dependent protein kinase (PKG), have been shown to decrease cyclins D1, A, and E expression in vascular smooth muscle cells. [68][69][70] CNP also blocks NGF-induced increases in p27 and increases in cdk4 in response to BDNF.…”

confidence: 94%

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

Simpson

Moon²,

Kleman

et al. 2007

Cell Cycle

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ACKnowlEdGEMEntSWe thank Amy Palmer for helpful discussions and reading of the manuscript, and Susan McTeer for manuscript preparation. This work was supported by grants NIDCD RO3 DC005704 to P.J.S., NIDCD RO1 DC02979 and NINDS RO1 NS39657 to G.V.R. AbStRACtNeuronal stem cell expansion and differentiation is a process involving stages of proliferation and maturation governed by the sequential and combinatorial exposure of cells to extrinsic factors. The olfactory epithelium is an excellent model to investigate regulation of this process, as it undergoes neuronal replacement post-natally. We have shown that the neurotrophins NGF and BDNF sequentially promote proliferation of developing olfactory sensory neuronal precursors, although their kinetics of proliferation and cell fate outcomes differ. Interestingly, CNP inhibits this neurotrophin-induced proliferation and promotes the maturation of these precursors to their next developmental stage. Here, we investigate the mechanisms behind these actions. Both NGF and BDNF increase the expression of cyclin D1 and cyclin-dependent kinase 4 (cdk4), with temporal expression patterns that parallel the proliferation kinetics of their cellular targets. The timing of cyclin D1 expression reflects differences in the need for transcription and translation in early and late stage precursors. CNP inhibits neurotrophin-induced cyclin D1 expression, and induces the expression of different profiles of inhibitory cell cycle proteins, which are neurotrophin-specific and correlate with the attainment of different maturational cell fates. Inhibition of protein degradation reverses the effects of neurotrophins and CNP on cyclin D1 and inhibitor expression levels, respectively. These results suggest a model for cell cycle regulation that involves the simultaneous expression of progressive and inhibitory cell cycle regulatory proteins in response to both proliferation and differentiation agents, followed by selective degradation of these proteins, providing a mechanism for rapid and exquisite control of the cell cycle.

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Overexpression of protein kinase G using adenovirus inhibits cyclin E transcription and mesangial cell cycle

Cited by 16 publications

References 35 publications

Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Nitric oxide negatively regulates proliferation and promotes neuronal differentiation through N-Myc downregulation

Quantitative analysis of the cardiac fibroblast transcriptome—implications for NO/cGMP signaling

Progressive and Inhibitory Cell Cycle Proteins Act Simultaneously to Regulate Neurotrophin-mediated Proliferation and Maturation of Neuronal Precursors

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