Abstract
BackgroundThe CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development. They function as context-dependent activators or repressors of transcription of their responsive genes, the promoters of which harbor the GTG(G/A)GAA consensus elements. Recently, several studies described Notch-independent activities of the CSL proteins.ResultsWe have identified putative CSL genes in several fungal species, showing that this family is not confined to metazoans. We have analyzed their sequence conservation and identified the presence of well-defined domains typical of genuine CSL proteins. Furthermore, we have shown that the candidate fungal protein sequences contain highly conserved regions known to be required for sequence-specific DNA binding in their metazoan counterparts. The phylogenetic analysis of the newly identified fungal CSL proteins revealed the existence of two distinct classes, both of which are present in all the species studied.ConclusionOur findings support the evolutionary origin of the CSL transcription factor family in the last common ancestor of fungi and metazoans. We hypothesize that the ancestral CSL function involved DNA binding and Notch-independent regulation of transcription and that this function may still be shared, to a certain degree, by the present CSL family members from both fungi and metazoans.
Highlights
The CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development
Nineteen putative CSL genes were found in seven organisms, with S. pombe and S. japonicus belonging to the Taphrinomycotina basal subphylum of ascomycetes, Rhizopus oryzae representing the zygomycetes and Coprinus cinereus, Cryptococcus neoformans, Phanerochaete chrysosporium and Ustilago maydis belonging to the basidiomycetes
We have shown the existence of CSL transcription factor family, known from studies of the metazoan Notch signaling pathway, in several fungal species
Summary
The CSL (CBF1/RBP-Jκ/Suppressor of Hairless/LAG-1) transcription factor family members are well-known components of the transmembrane receptor Notch signaling pathway, which plays a critical role in metazoan development. They function as context-dependent activators or repressors of transcription of their responsive genes, the promoters of which harbor the GTG(G/A)GAA consensus elements. CSL proteins recognize a very tightly defined consensus sequence GTG(G/A)GAA in target promoters Their best characterized function relates to the signaling pathway of the transmembrane receptor Notch where they mediate the effector nuclear step – activation of Notch-responsive genes. Its deregulation is implicated in several diseases including cancer [4] and, in addition, several (page number not for citation purposes)
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