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Regulation of the transforming growth factor β pathway by reversible ubiquitylation.

Al-Salihi MA, Herhaus L, Sapkota GP - Open Biol (2012)

Bottom Line: The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer.Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes.In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council-Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

ABSTRACT
The transforming growth factor β (TGFβ) signalling pathway plays a central role during embryonic development and in adult tissue homeostasis. It regulates gene transcription through a signalling cascade from cell surface receptors to intracellular SMAD transcription factors and their nuclear cofactors. The extent, duration and potency of signalling in response to TGFβ cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer. Reversible ubiquitylation of pathway components is a key regulatory process that plays a critical role in ensuring a balanced response to TGFβ signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFβ pathway components by ubiquitylation. Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes. In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.

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Regulation of SMAD transcription factors and nuclear cofactors by reversible ubiquitylation. An overview of how reversible ubiquitylation of SMAD transcription factors and associated nuclear cofactors may impact the SMAD-dependent transcription. Most of the reported E3s and DUBs known to regulate specific proteins are included. The reported mechanisms by which different E3 ubiquitin ligases and DUBs regulate SMAD proteins and associated cofactors are described in the text.
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RSOB120082F3: Regulation of SMAD transcription factors and nuclear cofactors by reversible ubiquitylation. An overview of how reversible ubiquitylation of SMAD transcription factors and associated nuclear cofactors may impact the SMAD-dependent transcription. Most of the reported E3s and DUBs known to regulate specific proteins are included. The reported mechanisms by which different E3 ubiquitin ligases and DUBs regulate SMAD proteins and associated cofactors are described in the text.

Mentions: SMAD proteins are the intracellular transducers of TGFβ signals. R-SMADs are phosphorylated at their C-terminal SXS motif inducing complex formation with SMAD4 and nuclear translocation. In the nucleus, they induce transcriptional responses of TGFβ target genes. Interfering with R-SMAD phosphorylation, stability, R-SMAD/SMAD4 complex formation or DNA binding would negatively impact TGFβ pathway signalling. Reversible ubiquitylation of SMADs directly impacts one or more of these attributes. Here, we provide an overview of how reversible ubiquitylation of SMAD transcription factors impacts SMAD function and pathway signalling. Figure 3 summarizes the key players regulating reversible ubiquitylation of SMADs.Figure 3.


Regulation of the transforming growth factor β pathway by reversible ubiquitylation.

Al-Salihi MA, Herhaus L, Sapkota GP - Open Biol (2012)

Regulation of SMAD transcription factors and nuclear cofactors by reversible ubiquitylation. An overview of how reversible ubiquitylation of SMAD transcription factors and associated nuclear cofactors may impact the SMAD-dependent transcription. Most of the reported E3s and DUBs known to regulate specific proteins are included. The reported mechanisms by which different E3 ubiquitin ligases and DUBs regulate SMAD proteins and associated cofactors are described in the text.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3376735&req=5

RSOB120082F3: Regulation of SMAD transcription factors and nuclear cofactors by reversible ubiquitylation. An overview of how reversible ubiquitylation of SMAD transcription factors and associated nuclear cofactors may impact the SMAD-dependent transcription. Most of the reported E3s and DUBs known to regulate specific proteins are included. The reported mechanisms by which different E3 ubiquitin ligases and DUBs regulate SMAD proteins and associated cofactors are described in the text.
Mentions: SMAD proteins are the intracellular transducers of TGFβ signals. R-SMADs are phosphorylated at their C-terminal SXS motif inducing complex formation with SMAD4 and nuclear translocation. In the nucleus, they induce transcriptional responses of TGFβ target genes. Interfering with R-SMAD phosphorylation, stability, R-SMAD/SMAD4 complex formation or DNA binding would negatively impact TGFβ pathway signalling. Reversible ubiquitylation of SMADs directly impacts one or more of these attributes. Here, we provide an overview of how reversible ubiquitylation of SMAD transcription factors impacts SMAD function and pathway signalling. Figure 3 summarizes the key players regulating reversible ubiquitylation of SMADs.Figure 3.

Bottom Line: The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer.Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes.In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.

View Article: PubMed Central - PubMed

Affiliation: Medical Research Council-Protein Phosphorylation Unit, Sir James Black Centre, University of Dundee, Dow Street, Dundee DD1 5EH, UK.

ABSTRACT
The transforming growth factor β (TGFβ) signalling pathway plays a central role during embryonic development and in adult tissue homeostasis. It regulates gene transcription through a signalling cascade from cell surface receptors to intracellular SMAD transcription factors and their nuclear cofactors. The extent, duration and potency of signalling in response to TGFβ cytokines are intricately regulated by complex biochemical processes. The corruption of these regulatory processes results in aberrant TGFβ signalling and leads to numerous human diseases, including cancer. Reversible ubiquitylation of pathway components is a key regulatory process that plays a critical role in ensuring a balanced response to TGFβ signals. Many studies have investigated the mechanisms by which various E3 ubiquitin ligases regulate the turnover and activity of TGFβ pathway components by ubiquitylation. Moreover, recent studies have shed new light into their regulation by deubiquitylating enzymes. In this report, we provide an overview of current understanding of the regulation of TGFβ signalling by E3 ubiquitin ligases and deubiquitylases.

Show MeSH
Related in: MedlinePlus