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

M Kitagawa; T Oyama; T Kawashima; B Yedvobnick; A Kumar; K Matsuno; K Harigaya

doi:10.1128/MCB.21.13.4337-4346.2001

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

Mol Cell Biol. 2001 Jul;21(13):4337-46. doi: 10.1128/MCB.21.13.4337-4346.2001.

Authors

M Kitagawa¹, T Oyama, T Kawashima, B Yedvobnick, A Kumar, K Matsuno, K Harigaya

Affiliation

¹ Department of Molecular and Tumor Pathology, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan. kitagawa@med.m.chiba-u.ac.jp

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

CSL receptor, human
DNA-Binding Proteins
Drosophila Proteins
Insect Proteins
MAML1 protein, human
Macromolecular Substances
Membrane Glycoproteins
Membrane Proteins
N protein, Drosophila
Nuclear Proteins
Receptors, Cell Surface
Receptors, Notch
Trans-Activators
Transcription Factors
mam protein, Drosophila

Associated data

GENBANK/D83785