Eintrag weiter verarbeiten
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transfo...
Gespeichert in:
| Zeitschriftentitel: | The FEBS Journal |
|---|---|
| Personen und Körperschaften: | , , , , , , , , , , |
| In: | The FEBS Journal, 276, 2009, 4, S. 1024-1035 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
Wiley
|
| Schlagwörter: |
| author_facet |
Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine |
|---|---|
| author |
Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine |
| spellingShingle |
Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine The FEBS Journal A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts Cell Biology Molecular Biology Biochemistry |
| author_sort |
blüthgen, nils |
| spelling |
Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine 1742-464X 1742-4658 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1111/j.1742-4658.2008.06846.x <jats:p>Mitogen‐activated protein kinase (MAPK) signaling determines crucial cell fate decisions in most cell types, and mediates cellular transformation in many types of cancer. The activity of MAPK is controlled by reversible phosphorylation, and the quantitative characteristics of MAPK activation determine the cellular response. Many systems biological studies have analyzed the activation kinetics and the dose–response behavior of the MAPK signaling pathway. Here we investigate how the pathway activity is controlled by transcriptional feedback loops. Initially, we predict that MAPK signaling regulates phosphatases, by integrating promoter sequence data and ontology‐based classification of gene function. From this, we deduce that MAPK signaling might be controlled by transcriptional negative feedback regulation via dual‐specificity phosphatases (DUSPs), and implement a mathematical model to further test this hypothesis. Using time‐resolved measurements of pathway activity and gene expression, we employ a model selection approach, and select DUSP6 as a highly likely candidate for shaping the activity of the MAPK pathway during cellular transformation caused by oncogenic RAS. Two predictions from the model were confirmed: first, feedback regulation requires that <jats:italic>DUSP6</jats:italic> mRNA and protein are unstable; and second, the activation kinetics of MAPK are ultrasensitive. Taken together, an integrated systems biological approach reveals that transcriptional negative feedback controls the kinetics and the extent of MAPK activation under both physiological and pathological conditions.</jats:p> A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts The FEBS Journal |
| doi_str_mv |
10.1111/j.1742-4658.2008.06846.x |
| facet_avail |
Online Free |
| finc_class_facet |
Biologie Chemie und Pharmazie |
| format |
ElectronicArticle |
| fullrecord |
blob:ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE3NDItNDY1OC4yMDA4LjA2ODQ2Lng |
| id |
ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE3NDItNDY1OC4yMDA4LjA2ODQ2Lng |
| institution |
DE-105 DE-14 DE-Ch1 DE-L229 DE-D275 DE-Bn3 DE-Brt1 DE-Zwi2 DE-D161 DE-Gla1 DE-Zi4 DE-15 DE-Pl11 DE-Rs1 |
| imprint |
Wiley, 2009 |
| imprint_str_mv |
Wiley, 2009 |
| issn |
1742-464X 1742-4658 |
| issn_str_mv |
1742-464X 1742-4658 |
| language |
English |
| mega_collection |
Wiley (CrossRef) |
| match_str |
bluthgen2009asystemsbiologicalapproachsuggeststhattranscriptionalfeedbackregulationbydualspecificityphosphatase6shapesextracellularsignalrelatedkinaseactivityinrastransformedfibroblasts |
| publishDateSort |
2009 |
| publisher |
Wiley |
| recordtype |
ai |
| record_format |
ai |
| series |
The FEBS Journal |
| source_id |
49 |
| title |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_unstemmed |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_full |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_fullStr |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_full_unstemmed |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_short |
A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_sort |
a systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in ras‐transformed fibroblasts |
| topic |
Cell Biology Molecular Biology Biochemistry |
| url |
http://dx.doi.org/10.1111/j.1742-4658.2008.06846.x |
| publishDate |
2009 |
| physical |
1024-1035 |
| description |
<jats:p>Mitogen‐activated protein kinase (MAPK) signaling determines crucial cell fate decisions in most cell types, and mediates cellular transformation in many types of cancer. The activity of MAPK is controlled by reversible phosphorylation, and the quantitative characteristics of MAPK activation determine the cellular response. Many systems biological studies have analyzed the activation kinetics and the dose–response behavior of the MAPK signaling pathway. Here we investigate how the pathway activity is controlled by transcriptional feedback loops. Initially, we predict that MAPK signaling regulates phosphatases, by integrating promoter sequence data and ontology‐based classification of gene function. From this, we deduce that MAPK signaling might be controlled by transcriptional negative feedback regulation via dual‐specificity phosphatases (DUSPs), and implement a mathematical model to further test this hypothesis. Using time‐resolved measurements of pathway activity and gene expression, we employ a model selection approach, and select DUSP6 as a highly likely candidate for shaping the activity of the MAPK pathway during cellular transformation caused by oncogenic RAS. Two predictions from the model were confirmed: first, feedback regulation requires that <jats:italic>DUSP6</jats:italic> mRNA and protein are unstable; and second, the activation kinetics of MAPK are ultrasensitive. Taken together, an integrated systems biological approach reveals that transcriptional negative feedback controls the kinetics and the extent of MAPK activation under both physiological and pathological conditions.</jats:p> |
| container_issue |
4 |
| container_start_page |
1024 |
| container_title |
The FEBS Journal |
| container_volume |
276 |
| format_de105 |
Article, E-Article |
| format_de14 |
Article, E-Article |
| format_de15 |
Article, E-Article |
| format_de520 |
Article, E-Article |
| format_de540 |
Article, E-Article |
| format_dech1 |
Article, E-Article |
| format_ded117 |
Article, E-Article |
| format_degla1 |
E-Article |
| format_del152 |
Buch |
| format_del189 |
Article, E-Article |
| format_dezi4 |
Article |
| format_dezwi2 |
Article, E-Article |
| format_finc |
Article, E-Article |
| format_nrw |
Article, E-Article |
| _version_ |
1792342871670521861 |
| geogr_code |
not assigned |
| last_indexed |
2024-03-01T16:42:42.565Z |
| geogr_code_person |
not assigned |
| openURL |
url_ver=Z39.88-2004&ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fvufind.svn.sourceforge.net%3Agenerator&rft.title=A+systems+biological+approach+suggests+that+transcriptional+feedback+regulation+by+dual%E2%80%90specificity+phosphatase%E2%80%836+shapes+extracellular+signal%E2%80%90related+kinase+activity+in+RAS%E2%80%90transformed+fibroblasts&rft.date=2009-02-01&genre=article&issn=1742-4658&volume=276&issue=4&spage=1024&epage=1035&pages=1024-1035&jtitle=The+FEBS+Journal&atitle=A+systems+biological+approach+suggests+that+transcriptional+feedback+regulation+by+dual%E2%80%90specificity+phosphatase%E2%80%836+shapes+extracellular+signal%E2%80%90related+kinase+activity+in+RAS%E2%80%90transformed+fibroblasts&aulast=Sers&aufirst=Christine&rft_id=info%3Adoi%2F10.1111%2Fj.1742-4658.2008.06846.x&rft.language%5B0%5D=eng |
| SOLR | |
| _version_ | 1792342871670521861 |
| author | Blüthgen, Nils, Legewie, Stefan, Kielbasa, Szymon M., Schramme, Anja, Tchernitsa, Oleg, Keil, Jana, Solf, Andrea, Vingron, Martin, Schäfer, Reinhold, Herzel, Hanspeter, Sers, Christine |
| author_facet | Blüthgen, Nils, Legewie, Stefan, Kielbasa, Szymon M., Schramme, Anja, Tchernitsa, Oleg, Keil, Jana, Solf, Andrea, Vingron, Martin, Schäfer, Reinhold, Herzel, Hanspeter, Sers, Christine, Blüthgen, Nils, Legewie, Stefan, Kielbasa, Szymon M., Schramme, Anja, Tchernitsa, Oleg, Keil, Jana, Solf, Andrea, Vingron, Martin, Schäfer, Reinhold, Herzel, Hanspeter, Sers, Christine |
| author_sort | blüthgen, nils |
| container_issue | 4 |
| container_start_page | 1024 |
| container_title | The FEBS Journal |
| container_volume | 276 |
| description | <jats:p>Mitogen‐activated protein kinase (MAPK) signaling determines crucial cell fate decisions in most cell types, and mediates cellular transformation in many types of cancer. The activity of MAPK is controlled by reversible phosphorylation, and the quantitative characteristics of MAPK activation determine the cellular response. Many systems biological studies have analyzed the activation kinetics and the dose–response behavior of the MAPK signaling pathway. Here we investigate how the pathway activity is controlled by transcriptional feedback loops. Initially, we predict that MAPK signaling regulates phosphatases, by integrating promoter sequence data and ontology‐based classification of gene function. From this, we deduce that MAPK signaling might be controlled by transcriptional negative feedback regulation via dual‐specificity phosphatases (DUSPs), and implement a mathematical model to further test this hypothesis. Using time‐resolved measurements of pathway activity and gene expression, we employ a model selection approach, and select DUSP6 as a highly likely candidate for shaping the activity of the MAPK pathway during cellular transformation caused by oncogenic RAS. Two predictions from the model were confirmed: first, feedback regulation requires that <jats:italic>DUSP6</jats:italic> mRNA and protein are unstable; and second, the activation kinetics of MAPK are ultrasensitive. Taken together, an integrated systems biological approach reveals that transcriptional negative feedback controls the kinetics and the extent of MAPK activation under both physiological and pathological conditions.</jats:p> |
| doi_str_mv | 10.1111/j.1742-4658.2008.06846.x |
| facet_avail | Online, Free |
| finc_class_facet | Biologie, Chemie und Pharmazie |
| format | ElectronicArticle |
| format_de105 | Article, E-Article |
| format_de14 | Article, E-Article |
| format_de15 | Article, E-Article |
| format_de520 | Article, E-Article |
| format_de540 | Article, E-Article |
| format_dech1 | Article, E-Article |
| format_ded117 | Article, E-Article |
| format_degla1 | E-Article |
| format_del152 | Buch |
| format_del189 | Article, E-Article |
| format_dezi4 | Article |
| format_dezwi2 | Article, E-Article |
| format_finc | Article, E-Article |
| format_nrw | Article, E-Article |
| geogr_code | not assigned |
| geogr_code_person | not assigned |
| id | ai-49-aHR0cDovL2R4LmRvaS5vcmcvMTAuMTExMS9qLjE3NDItNDY1OC4yMDA4LjA2ODQ2Lng |
| imprint | Wiley, 2009 |
| imprint_str_mv | Wiley, 2009 |
| institution | DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161, DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1 |
| issn | 1742-464X, 1742-4658 |
| issn_str_mv | 1742-464X, 1742-4658 |
| language | English |
| last_indexed | 2024-03-01T16:42:42.565Z |
| match_str | bluthgen2009asystemsbiologicalapproachsuggeststhattranscriptionalfeedbackregulationbydualspecificityphosphatase6shapesextracellularsignalrelatedkinaseactivityinrastransformedfibroblasts |
| mega_collection | Wiley (CrossRef) |
| physical | 1024-1035 |
| publishDate | 2009 |
| publishDateSort | 2009 |
| publisher | Wiley |
| record_format | ai |
| recordtype | ai |
| series | The FEBS Journal |
| source_id | 49 |
| spelling | Blüthgen, Nils Legewie, Stefan Kielbasa, Szymon M. Schramme, Anja Tchernitsa, Oleg Keil, Jana Solf, Andrea Vingron, Martin Schäfer, Reinhold Herzel, Hanspeter Sers, Christine 1742-464X 1742-4658 Wiley Cell Biology Molecular Biology Biochemistry http://dx.doi.org/10.1111/j.1742-4658.2008.06846.x <jats:p>Mitogen‐activated protein kinase (MAPK) signaling determines crucial cell fate decisions in most cell types, and mediates cellular transformation in many types of cancer. The activity of MAPK is controlled by reversible phosphorylation, and the quantitative characteristics of MAPK activation determine the cellular response. Many systems biological studies have analyzed the activation kinetics and the dose–response behavior of the MAPK signaling pathway. Here we investigate how the pathway activity is controlled by transcriptional feedback loops. Initially, we predict that MAPK signaling regulates phosphatases, by integrating promoter sequence data and ontology‐based classification of gene function. From this, we deduce that MAPK signaling might be controlled by transcriptional negative feedback regulation via dual‐specificity phosphatases (DUSPs), and implement a mathematical model to further test this hypothesis. Using time‐resolved measurements of pathway activity and gene expression, we employ a model selection approach, and select DUSP6 as a highly likely candidate for shaping the activity of the MAPK pathway during cellular transformation caused by oncogenic RAS. Two predictions from the model were confirmed: first, feedback regulation requires that <jats:italic>DUSP6</jats:italic> mRNA and protein are unstable; and second, the activation kinetics of MAPK are ultrasensitive. Taken together, an integrated systems biological approach reveals that transcriptional negative feedback controls the kinetics and the extent of MAPK activation under both physiological and pathological conditions.</jats:p> A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts The FEBS Journal |
| spellingShingle | Blüthgen, Nils, Legewie, Stefan, Kielbasa, Szymon M., Schramme, Anja, Tchernitsa, Oleg, Keil, Jana, Solf, Andrea, Vingron, Martin, Schäfer, Reinhold, Herzel, Hanspeter, Sers, Christine, The FEBS Journal, A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts, Cell Biology, Molecular Biology, Biochemistry |
| title | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_full | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_fullStr | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_full_unstemmed | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_short | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| title_sort | a systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in ras‐transformed fibroblasts |
| title_unstemmed | A systems biological approach suggests that transcriptional feedback regulation by dual‐specificity phosphatase 6 shapes extracellular signal‐related kinase activity in RAS‐transformed fibroblasts |
| topic | Cell Biology, Molecular Biology, Biochemistry |
| url | http://dx.doi.org/10.1111/j.1742-4658.2008.06846.x |