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The CSL proteins, versatile transcription factors and context dependent corepressors of the notch signaling pathway

View Article: PubMed Central - PubMed

ABSTRACT

The Notch signaling pathway is a reiteratively used cell to cell communication pathway that triggers pleiotropic effects. The correct regulation of the pathway permits the efficient regulation of genes involved in cell fate decision throughout development. This activity relies notably on the CSL proteins, (an acronym for CBF-1/RBPJ-κ in Homo sapiens/Mus musculus respectively, Suppressor of Hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis elegans) which is the unique transcription factor and DNA binding protein involved in this pathway. The CSL proteins have the capacity to recruit activation or repression complexes according to the cellular context. The aim of this review is to describe the different co-repressor proteins that interact directly with CSL proteins to form repression complexes thereby regulating the Notch signaling pathway in animal cells to give insights into the paralogous evolution of these co-repressors in higher eumetazoans and their subsequent effects at developmental processes.

No MeSH data available.


Comparative view of the repression and activation complexes. One of the best known models of the NSP is Drosophila melanogaster. CSL transcription factor acts as a bridging protein between the DNA and a complex of proteins intended to modify chromatin topology in a specific locus. In the case of the gene repression complex, CSL recruits H that in turn will form a HDAC together with Gro and CtBP. Even if H is the main co-repressor of the pathway in the fly fruit, no H homolog has been found in models out of insects, but instead a series of other proteins seem to take this function as we will see further. For the gene activation complex, NICD and Mam occupied the CSL’s domains and, in turns, recruit a HAT complex to generate an open chromatin topology and promote gene expression. Activation complexes seem to be similar in all models where NSP has been studied. Skip is common in both complexes
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Fig3: Comparative view of the repression and activation complexes. One of the best known models of the NSP is Drosophila melanogaster. CSL transcription factor acts as a bridging protein between the DNA and a complex of proteins intended to modify chromatin topology in a specific locus. In the case of the gene repression complex, CSL recruits H that in turn will form a HDAC together with Gro and CtBP. Even if H is the main co-repressor of the pathway in the fly fruit, no H homolog has been found in models out of insects, but instead a series of other proteins seem to take this function as we will see further. For the gene activation complex, NICD and Mam occupied the CSL’s domains and, in turns, recruit a HAT complex to generate an open chromatin topology and promote gene expression. Activation complexes seem to be similar in all models where NSP has been studied. Skip is common in both complexes

Mentions: While the activator complex seems to be widely conserved in its structure and function, the repression complex is surprisingly diverse in the different species where the NSP has been described [17]. But what exactly is the role of the repression complex? In the absence of NICD the CSL transcription factor functions as a transcriptional repressor in a “default repression” fashion. In this case CSL recruits co-repressor proteins such as Hairless (H) [22], C-terminal binding protein (CtBP), Groucho (Gro) [23, 24] and Insensitive [25] in D. melanogaster or SMRT/NCoR, CIR, KyoT proteins, SHARP/MINT in mammals [26, 27] as well as Sin3A and KDM5a and histone deacetylases (HDAC) [6, 9, 18, 28, 29]. This activity switch depends on the precise cellular context during the regulatory process which implies conformational chromatin variations caused by quick exchange between factors required to activate or repress transcription [3, 5, 18, 30] (Fig. 3).Fig. 3


The CSL proteins, versatile transcription factors and context dependent corepressors of the notch signaling pathway
Comparative view of the repression and activation complexes. One of the best known models of the NSP is Drosophila melanogaster. CSL transcription factor acts as a bridging protein between the DNA and a complex of proteins intended to modify chromatin topology in a specific locus. In the case of the gene repression complex, CSL recruits H that in turn will form a HDAC together with Gro and CtBP. Even if H is the main co-repressor of the pathway in the fly fruit, no H homolog has been found in models out of insects, but instead a series of other proteins seem to take this function as we will see further. For the gene activation complex, NICD and Mam occupied the CSL’s domains and, in turns, recruit a HAT complex to generate an open chromatin topology and promote gene expression. Activation complexes seem to be similar in all models where NSP has been studied. Skip is common in both complexes
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Related In: Results  -  Collection

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Fig3: Comparative view of the repression and activation complexes. One of the best known models of the NSP is Drosophila melanogaster. CSL transcription factor acts as a bridging protein between the DNA and a complex of proteins intended to modify chromatin topology in a specific locus. In the case of the gene repression complex, CSL recruits H that in turn will form a HDAC together with Gro and CtBP. Even if H is the main co-repressor of the pathway in the fly fruit, no H homolog has been found in models out of insects, but instead a series of other proteins seem to take this function as we will see further. For the gene activation complex, NICD and Mam occupied the CSL’s domains and, in turns, recruit a HAT complex to generate an open chromatin topology and promote gene expression. Activation complexes seem to be similar in all models where NSP has been studied. Skip is common in both complexes
Mentions: While the activator complex seems to be widely conserved in its structure and function, the repression complex is surprisingly diverse in the different species where the NSP has been described [17]. But what exactly is the role of the repression complex? In the absence of NICD the CSL transcription factor functions as a transcriptional repressor in a “default repression” fashion. In this case CSL recruits co-repressor proteins such as Hairless (H) [22], C-terminal binding protein (CtBP), Groucho (Gro) [23, 24] and Insensitive [25] in D. melanogaster or SMRT/NCoR, CIR, KyoT proteins, SHARP/MINT in mammals [26, 27] as well as Sin3A and KDM5a and histone deacetylases (HDAC) [6, 9, 18, 28, 29]. This activity switch depends on the precise cellular context during the regulatory process which implies conformational chromatin variations caused by quick exchange between factors required to activate or repress transcription [3, 5, 18, 30] (Fig. 3).Fig. 3

View Article: PubMed Central - PubMed

ABSTRACT

The Notch signaling pathway is a reiteratively used cell to cell communication pathway that triggers pleiotropic effects. The correct regulation of the pathway permits the efficient regulation of genes involved in cell fate decision throughout development. This activity relies notably on the CSL proteins, (an acronym for CBF-1/RBPJ-κ in Homo sapiens/Mus musculus respectively, Suppressor of Hairless in Drosophila melanogaster, Lag-1 in Caenorhabditis elegans) which is the unique transcription factor and DNA binding protein involved in this pathway. The CSL proteins have the capacity to recruit activation or repression complexes according to the cellular context. The aim of this review is to describe the different co-repressor proteins that interact directly with CSL proteins to form repression complexes thereby regulating the Notch signaling pathway in animal cells to give insights into the paralogous evolution of these co-repressors in higher eumetazoans and their subsequent effects at developmental processes.

No MeSH data available.