RRC ID 4782
Author Kitagawa M, Oyama T, Kawashima T, Yedvobnick B, Kumar A, Matsuno K, Harigaya K.
Title A human protein with sequence similarity to Drosophila mastermind coordinates the nuclear form of notch and a CSL protein to build a transcriptional activator complex on target promoters.
Journal Mol Cell Biol
Abstract Mastermind (Mam) has been implicated as an important positive regulator of the Notch signaling pathway by genetic studies using Drosophila melanogaster. Here we describe a biochemical mechanism of action of Mam within the Notch signaling pathway. Expression of a human sequence related to Drosophila Mam (hMam-1) in mammalian cells augments induction of Hairy Enhancer of split (HES) promoters by Notch signaling. hMam-1 stabilizes and participates in the DNA binding complex of the intracellular domain of human Notch1 and a CSL protein. Truncated versions of hMam-1 that can maintain an association with the complex behave in a dominant negative fashion and depress transactivation. Furthermore, Drosophila Mam forms a similar complex with the intracellular domain of Drosophila Notch and Drosophila CSL protein during activation of Enhancer of split, the Drosophila counterpart of HES. These results indicate that Mam is an essential component of the transcriptional apparatus of Notch signaling.
Volume 21(13)
Pages 4337-46
Published 2001-7-1
DOI 10.1128/MCB.21.13.4337-4346.2001
PMID 11390662
PMC PMC87094
MeSH Amino Acid Sequence Animals Cell Line DNA-Binding Proteins / chemistry DNA-Binding Proteins / genetics DNA-Binding Proteins / metabolism* Drosophila Proteins* Drosophila melanogaster / genetics Gene Expression Regulation Humans Insect Proteins / chemistry Insect Proteins / genetics Insect Proteins / metabolism Macromolecular Substances Membrane Glycoproteins* Membrane Proteins / genetics Membrane Proteins / metabolism* Microscopy, Fluorescence Molecular Sequence Data Nuclear Proteins / chemistry Nuclear Proteins / genetics Nuclear Proteins / metabolism* Promoter Regions, Genetic* Protein Structure, Tertiary Receptors, Cell Surface / genetics Receptors, Cell Surface / metabolism Receptors, Notch Sequence Alignment Signal Transduction* Trans-Activators Transcription Factors Transcriptional Activation Transfection
IF 3.611
Times Cited 86
DNA material RBP-J (RDB01801)