The Notch signaling pathway regulates genes involved in cell fate decision throughout development. Its activity relies notably on the CSL transcription factors. BEND6 is a BEN-solo (bears a single BEN domain) factor that binds CSL via its BEN domain and acts as a CSL co-repressor. BEND6 associates with and represses Notch target genes, antagonizing Notch signaling in neural stem cells, thereby opposing their self-renewal and promoting neurogenesis [].
The CLS family (CBF1/RBP-Jkappa/suppressor of hairless) consists of transcription factors essential for metazoan development, mainly due to their involvement in the Notch pathway []. The members of this family recognize and bind to response element (GTGA/GGAA) in the promoters of the genes they regulate []. Despite lacking the Notch pathway, CSL family members have been identified in fungal species. Schizosaccharomyces pombe has two CLS family proteins, Cbf11 and Cbf12, that bind the canonical CSL response element and play opposing roles in cell adhesion and coordination of cell and nuclear division [, ].
Corepressor interacting with RBPJ 1 (CIR1, also known as recepin) interacts CBF1, which is a member of the CSL family of DNA binding factors, which mediate either transcriptional repression or transcriptional activation. CIR1 binds to histone deacetylase and to SAP30 and serves as a linker between CBF1 and the histone deacetylase complex []. It interacts with a variety of proteins, including Epstein-Barr virus RPMS1 []and the NKAP transcriptional repressor of notch signaling [].
This entry represents the N-terminal domain found in a family of neurogenic mastermind-like proteins (MAMLs), which act as critical transcriptional co-activators for Notch signaling [, , ]. Notch receptors are cleaved upon ligand engagement and the intracellular domain of Notch shuttles to the nucleus. MAMLs form a functional DNA-binding complex with the cleaved Notch receptor and the transcription factor CSL, thereby regulating transcriptional events that are specific to the Notch pathway. MAML proteins may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C) [], tumour suppressor pathway (p53) []and colon carcinoma survival (beta-catenin) []. MAML proteins could mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.The N-terminal domain of MAML proteins adopt an elongated kinked helix that wraps around ANK and CSL forming one of the complexes in the build-up of the Notch transcriptional complex for recruiting general transcription factors []. This N-terminal domain is responsible for its interaction with the ankyrin repeat region of the Notch proteins NOTCH1 [], NOTCH2 [], NOTCH3 []and NOTCH4. It forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1, and also binds CREBBP/CBP []and CDK8 []. The C-terminal region is required for transcriptional activation.
This family includes the neurogenic mastermind-like proteins 1-3 (MAML1-3) from chordates, which act as critical transcriptional co-activators for Notch signaling [, ]. Notch receptors are cleaved upon ligand engagement and the intracellular domain of Notch shuttles to the nucleus. MAMLs form a functional DNA-binding complex with the cleaved Notch receptor and the transcription factor CSL, thereby regulating transcriptional events that are specific to the Notch pathway. MAML proteins may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C) [], tumour suppressor pathway (p53) []and colon carcinoma survival (beta-catenin) []. MAML proteins could mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.They consist of an N-terminal domain which adopt an elongated kinked helix that wraps around ANK and CSL forming one of the complexes in the build-up of the Notch transcriptional complex for recruiting general transcription factors [, ]]. This N-terminal domain is responsible for its interaction with the ankyrin repeat region of the Notch proteins NOTCH1 [], NOTCH2 [], NOTCH3 []and NOTCH4. It forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1, and also binds CREBBP/CBP []and CDK8 []. The C-terminal region is required for transcriptional activation.
This entry represents the N-terminal domain found in a family of neurogenic mastermind-like proteins (MAMLs), which act as critical transcriptional co-activators for Notch signaling [, , ]. Notch receptors are cleaved upon ligand engagement and the intracellular domain of Notch shuttles to the nucleus. MAMLs form a functional DNA-binding complex with the cleaved Notch receptor and the transcription factor CSL, thereby regulating transcriptional events that are specific to the Notch pathway. MAML proteins may also play roles as key transcriptional co-activators in other signal transduction pathways as well, including: muscle differentiation and myopathies (MEF2C) [], tumour suppressor pathway (p53) []and colon carcinoma survival (beta-catenin) []. MAML proteins could mediate cross-talk among the various signaling pathways and the diverse activities of the MAML proteins converge to impact normal biological processes and human diseases, including cancers.The N-terminal domain of MAML proteins adopt an elongated kinked helix that wraps around ANK and CSL forming one of the complexes in the build-up of the Notch transcriptional complex for recruiting general transcription factors []. This N-terminal domain is responsible for its interaction with the ankyrin repeat region of the Notch proteins NOTCH1 [], NOTCH2 [], NOTCH3 []and NOTCH4. It forms a DNA-binding complex with Notch proteins and RBPSUH/RBP-J kappa/CBF1, and also binds CREBBP/CBP []and CDK8 []. The C-terminal region is required for transcriptional activation.
