NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals []. NOD (NOTCH protein domain) represents a region present in many NOTCH proteins and NOTCH homologues in multiple species such as 0, NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. Role of NOD domain remains to be elucidated.
NOTCH signalling plays a fundamental role during a great number of developmental processes in multicellular animals []. NOD and NODP represent a region present in many NOTCH proteins and NOTCH homologues in multiple species such as NOTCH2 and NOTCH3, LIN12, SC1 and TAN1. The role of the NOD and NODP domains remains to be elucidated.
This entry includes arginine vasopressin-induced protein 1 (Avpi1) and C8orf4 protein. Avpi1 is thought to be involved in MAP kinase activation, epithelial sodium channel (ENaC) down-regulation and cell cycling []. C8orf4, also known as transcriptional and immune response regulator (TCIM) or thyroid cancer 1 (TC-1), plays important roles in many signalling pathways, such as Wnt/beta-catenin signalling pathway, and is involved in the development of many cancers []. C8orf4 also suppresses NOTCH2 signalling in liver cancer stem cells [].
Transcriptional and immune response regulator (Tcim; also known as C8orf4 or TC1) is a regulator implicated in cancer and inflammation []. It is highly expressed in several tumours and implicated in tumorigenesis. It plays a role in the mitogen-activated MAPK2/3 signaling pathway, and positively regulates G1-to-S-phase transition of the cell cycle []. It negatively regulates the self-renewal of liver cancer stem cells via suppression of NOTCH2 signalling [].
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.
