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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.


KyoT-CSL. The interaction of KyoT 1 and 3 proteins with the transcription factor is mapped at the central region of CSL. This interaction still proposed the exclusive and antagonistic competition between the co-activators and the co-repressor in the NSP. Concentration of the KyoT proteins seems to play also an important role in the regulation control of genes expression, which are commune characteristics of the repression complexes in this signaling context
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Fig6: KyoT-CSL. The interaction of KyoT 1 and 3 proteins with the transcription factor is mapped at the central region of CSL. This interaction still proposed the exclusive and antagonistic competition between the co-activators and the co-repressor in the NSP. Concentration of the KyoT proteins seems to play also an important role in the regulation control of genes expression, which are commune characteristics of the repression complexes in this signaling context

Mentions: KyoT 2 (containing LIM1 and 2 domains) and KyoT 3 (containing LIM1, 2 and 3 domains) proteins, but not KyoT 1 protein, possess the singularity to interact with RBPJ-κ protein [93, 96]. Interaction occurs at the central region of RBPJ-κ, the BTD (Fig. 6). The DNA-bound activator complex of NSP has been solved in great detail: the NTD and the BTD of CSL make the DNA contacts, whereas the BTD and the CTD bind to NICD and Mam. Thus the BTD is critical for activator and repressor complex formation alike. The interaction between KyoT/RBPJ-κ and NICD/RBPJ-κ are exclusive and antagonistic [93, 95, 96]. This way, KyoT 2 has the capacity to antagonize the gene expression mediated by NICD in a concentration-dependent manner. In other words, when the KyoT 2 concentration increases inside the cell nucleus, it can provoke a sequential gene inactivation of Notch dependent genes, because the KyoT 2 competes with NICD for the binding of RBPJ-κ [93, 96]. KyoT 3 likewise binds RBPJ-κ and inhibits Hes-1 gene activation, a prime Notch target gene which encodes a bHLH transcriptional repressor [94]. These data together could mean that both proteins, KyoT 2 and KyoT 3, truly work by antagonizing gene expression under NSP control, but in a different temporality that gives as result a different grade of cellular specialization.Fig. 6


The CSL proteins, versatile transcription factors and context dependent corepressors of the notch signaling pathway
KyoT-CSL. The interaction of KyoT 1 and 3 proteins with the transcription factor is mapped at the central region of CSL. This interaction still proposed the exclusive and antagonistic competition between the co-activators and the co-repressor in the NSP. Concentration of the KyoT proteins seems to play also an important role in the regulation control of genes expression, which are commune characteristics of the repression complexes in this signaling context
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC5037638&req=5

Fig6: KyoT-CSL. The interaction of KyoT 1 and 3 proteins with the transcription factor is mapped at the central region of CSL. This interaction still proposed the exclusive and antagonistic competition between the co-activators and the co-repressor in the NSP. Concentration of the KyoT proteins seems to play also an important role in the regulation control of genes expression, which are commune characteristics of the repression complexes in this signaling context
Mentions: KyoT 2 (containing LIM1 and 2 domains) and KyoT 3 (containing LIM1, 2 and 3 domains) proteins, but not KyoT 1 protein, possess the singularity to interact with RBPJ-κ protein [93, 96]. Interaction occurs at the central region of RBPJ-κ, the BTD (Fig. 6). The DNA-bound activator complex of NSP has been solved in great detail: the NTD and the BTD of CSL make the DNA contacts, whereas the BTD and the CTD bind to NICD and Mam. Thus the BTD is critical for activator and repressor complex formation alike. The interaction between KyoT/RBPJ-κ and NICD/RBPJ-κ are exclusive and antagonistic [93, 95, 96]. This way, KyoT 2 has the capacity to antagonize the gene expression mediated by NICD in a concentration-dependent manner. In other words, when the KyoT 2 concentration increases inside the cell nucleus, it can provoke a sequential gene inactivation of Notch dependent genes, because the KyoT 2 competes with NICD for the binding of RBPJ-κ [93, 96]. KyoT 3 likewise binds RBPJ-κ and inhibits Hes-1 gene activation, a prime Notch target gene which encodes a bHLH transcriptional repressor [94]. These data together could mean that both proteins, KyoT 2 and KyoT 3, truly work by antagonizing gene expression under NSP control, but in a different temporality that gives as result a different grade of cellular specialization.Fig. 6

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.