RRC ID 28439
Author Kuroda K, Tani S, Tamura K, Minoguchi S, Kurooka H, Honjo T.
Title Delta-induced Notch signaling mediated by RBP-J inhibits MyoD expression and myogenesis.
Journal J Biol Chem
Abstract Signaling induced by interaction between the receptor Notch and its ligand Delta plays an important role in cell fate determination in vertebrates as well as invertebrates. Vertebrate Notch signaling has been investigated using its constitutively active form, i.e. the truncated intracellular region which is believed to mimic Notch-Delta signaling by interaction with a DNA-binding protein RBP-J. However, the molecular mechanism for Notch signaling triggered by ligand binding, which leads to inhibition of differentiation, is not clear. We have established a myeloma cell line expressing mouse Delta1 on its cell surface which can block muscle differentiation by co-culture with C2C12 muscle progenitor cells. We showed that Delta-induced Notch signaling stimulated transcriptional activation of RBP-J binding motif, containing promoters including the HES1 promoter. Furthermore, ligand-induced Notch signaling up-regulated HES1 mRNA expression within 1 h and subsequently reduced expression of MyoD mRNA. Since cycloheximide treatment did not inhibit induction of HES1 mRNA, the HES1 promoter appears to be a primary target of activated Notch. In addition, a transcriptionally active form of RBP-J, i.e. VP16-RBP-J, inhibited muscle differentiation of C2C12 cells by blocking the expression of MyoD protein. These results suggest that HES1 induction by the Delta1/Notch signaling is mediated by RBP-J and blocks myogenic differentiation of C2C12 cells by subsequent inhibition of MyoD expression.
Volume 274(11)
Pages 7238-44
Published 1999-3-12
DOI 10.1074/jbc.274.11.7238
PII S0021-9258(18)36996-5
PMID 10066785
MeSH Animals Base Sequence DNA Primers DNA-Binding Proteins / metabolism* Gene Expression Regulation / physiology* Immunoglobulin J Recombination Signal Sequence-Binding Protein Intracellular Signaling Peptides and Proteins Membrane Proteins / metabolism* Membrane Proteins / physiology* Mice Muscle Development* MyoD Protein / genetics* Nuclear Proteins* RNA, Messenger / genetics Receptor, Notch1 Receptors, Cell Surface* Signal Transduction* Transcription Factors* Tumor Cells, Cultured Up-Regulation
IF 4.238
Times Cited 204
DNA material pCMX-N/RBP-J (RDB03021) pCMX-N/VP16-RBP-J (RDB03023)