Role of Deltex-1 as a Transcriptional Regulator Downstream of the Notch Receptor

• Published in: The Journal of biological chemistry Vol. 276; no. 48; pp. 45031 - 45040
• Main Authors: Yamamoto, N, Yamamoto, S, Inagaki, F, Kawaichi, M, Fukamizu, A, Kishi, N, Matsuno, K, Nakamura, K, Weinmaster, G, Okano, H, Nakafuku, M
• Format: Journal Article
• Language: English
• Published: United States American Society for Biochemistry and Molecular Biology 30.11.2001
• Subjects: Animals; Basic Helix-Loop-Helix Transcription Factors; Blotting, Western; Carrier Proteins; Cell Differentiation; Cell Line; Cell Nucleus - metabolism; COS Cells; Deltex-1 protein; DNA, Complementary - metabolism; DNA-Binding Proteins - metabolism; Drosophila melanogaster; Drosophila Proteins; DTX1 protein; E1A-Associated p300 Protein; Gene Deletion; Genes, Reporter; Humans; Immunohistochemistry; Membrane Proteins - metabolism; Membrane Proteins - physiology; Mice; Mutagenesis; Notch receptors; Nuclear Proteins - metabolism; p300 protein; Plasmids - metabolism; Precipitin Tests; Protein Binding; Proteins - metabolism; Proteins - physiology; Rats; Receptors, Notch; Signal Transduction; Trans-Activators - metabolism; Transcription Factors - metabolism; Transcription, Genetic; Transcriptional Activation; Transfection
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M105245200

Intercellular signaling through the cell-surface receptor Notch plays important roles in a variety of developmental processes as well as in pathogenesis of some human cancers and genetic disorders. However, the mechanisms by which Notch signals are transduced into cells still remain elusive. Here we investigated the signaling mechanisms for Notch in the cell fate control of neural progenitor cells. We show that Deltex-1 (DTX1), a mammalian homolog of Drosophila Deltex, mediates a Notch signal to block differentiation of neural progenitor cells. We found that a significant fraction of DTX1 proteins were localized in the nucleus and physically interacted with the transcriptional coactivator p300. Through its binding to p300, DTX1 inhibited transcriptional activation by the neural-specific helix-loop-helix-type transcription factor MASH1, and this mechanism is likely responsible for the differentiation inhibition of neural progenitor cells. Our results further suggest that DTX1 regulates transcription independently of the previously characterized Notch signaling pathway involving RBP-J and HES1/HES5. Thus, DTX1 serves as an important signaling component downstream of Notch that regulates transcription in the nucleus.