Saul, Meike J. ; Groher, Florian ; Hegewald, Anett B. ; Müller-McNicoll, Michaela ; Marschalek, Rolf ; Suess, Beatrix ; Steinhilber, Dieter (2017)
TGFβ/SMAD signalling modulates MLL and MLL-AF4 mediated 5-lipoxygenase promoter activation.
In: Prostaglandins & other lipid mediators, 133
Artikel, Bibliographie
Kurzbeschreibung (Abstract)
5-Lipoxygenase (5-LO) catalyzes the initial two steps of the conversion of arachidonic acid to leukotrienes which represent a group of pro-inflammatory lipid mediators involved in immune defense reactions as well as inflammation, allergy and cancer. Transforming growth factor-β (TGFβ) and calcitriol strongly upregulate 5-LO expression during myeloid cell differentiation and MLL-AF4 has been shown to strongly activate the 5-LO promoter. Here, we investigated the role of TGFβ/SMAD signalling in 5-LO promoter activation. We identified two functional SMAD binding elements in the proximal part of the 5-LO promoter which significantly induce 5-LO promoter activity via TGFβ and SMAD3/4. Since aberrant 5-LO gene expression has been linked with mixed lineage leukemia (MLL) which is characterized by the presence of MLL fusion proteins (e.g. MLL-AF4), we also investigated the influence of TGFβ/SMADs on MLL- and MLL-AF4-mediated 5-LO promoter activation. Our data show that induction of 5-LO promoter activity by SMAD3/4 is MLL-dependent and that knockdown of the MLL complex component MEN1 attenuates the SMAD effect. Our data suggest that induction of 5-LO gene expression by TGFβ is at least in part due to stimulation of transcript initiation.
| Typ des Eintrags: | Artikel |
|---|---|
| Erschienen: | 2017 |
| Autor(en): | Saul, Meike J. ; Groher, Florian ; Hegewald, Anett B. ; Müller-McNicoll, Michaela ; Marschalek, Rolf ; Suess, Beatrix ; Steinhilber, Dieter |
| Art des Eintrags: | Bibliographie |
| Titel: | TGFβ/SMAD signalling modulates MLL and MLL-AF4 mediated 5-lipoxygenase promoter activation. |
| Sprache: | Englisch |
| Publikationsjahr: | November 2017 |
| Titel der Zeitschrift, Zeitung oder Schriftenreihe: | Prostaglandins & other lipid mediators |
| Jahrgang/Volume einer Zeitschrift: | 133 |
| Kurzbeschreibung (Abstract): | 5-Lipoxygenase (5-LO) catalyzes the initial two steps of the conversion of arachidonic acid to leukotrienes which represent a group of pro-inflammatory lipid mediators involved in immune defense reactions as well as inflammation, allergy and cancer. Transforming growth factor-β (TGFβ) and calcitriol strongly upregulate 5-LO expression during myeloid cell differentiation and MLL-AF4 has been shown to strongly activate the 5-LO promoter. Here, we investigated the role of TGFβ/SMAD signalling in 5-LO promoter activation. We identified two functional SMAD binding elements in the proximal part of the 5-LO promoter which significantly induce 5-LO promoter activity via TGFβ and SMAD3/4. Since aberrant 5-LO gene expression has been linked with mixed lineage leukemia (MLL) which is characterized by the presence of MLL fusion proteins (e.g. MLL-AF4), we also investigated the influence of TGFβ/SMADs on MLL- and MLL-AF4-mediated 5-LO promoter activation. Our data show that induction of 5-LO promoter activity by SMAD3/4 is MLL-dependent and that knockdown of the MLL complex component MEN1 attenuates the SMAD effect. Our data suggest that induction of 5-LO gene expression by TGFβ is at least in part due to stimulation of transcript initiation. |
| ID-Nummer: | pmid:28803964 |
| Fachbereich(e)/-gebiet(e): | 10 Fachbereich Biologie 10 Fachbereich Biologie > Synthetic Genetic Circuits (2020 umbenannt in "Synthetic RNA biology") |
| Hinterlegungsdatum: | 29 Aug 2017 06:18 |
| Letzte Änderung: | 16 Jan 2018 08:40 |
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