Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo Journal Article
| Authors: | Oyama, T.; Harigaya, K.; Sasaki, N.; Okamura, Y.; Kokubo, H.; Saga, Y.; Hozumi, K.; Suganami, A.; Tamura, Y.; Nagase, T.; Koga, H.; Nishimura, M.; Sakamoto, R.; Sato, M.; Yoshida, N.; Kitagawa, M. |
| Article Title: | Mastermind-like 1 (MamL1) and mastermind-like 3 (MamL3) are essential for Notch signaling in vivo |
| Abstract: | Mastermind (Mam) is one of the elements of Notch signaling, a system that plays a pivotal role in metazoan development. Mam proteins form transcriptionally activating complexes with the intracellular domains of Notch, which are generated in response to the ligand-receptor interaction, and CSL DNA-binding proteins. In mammals, three structurally divergent Mam isoforms (MamL1, MamL2 and MamL3) have been identified. There have also been indications that Mam interacts functionally with various other transcription factors, including the p53 tumor suppressor, β-catenin and NF-κB. We have demonstrated previously that disruption of MamL1 causes partial deficiency of Notch signaling in vivo. However, MamL1-deficient mice did not recapitulate total loss of Notch signaling, suggesting that other members could compensate for the loss or that Notch signaling could proceed in the absence of Mam in certain contexts. Here, we report the generation of lines of mice null for MamL3. Although MamL3-null mice showed no apparent abnormalities, mice null for both MamL1 and MamL3 died during the early organogenic period with classic pan-Notch defects. Furthermore, expression of the lunatic fringe gene, which is strictly controlled by Notch signaling in the posterior presomitic mesoderm, was undetectable in this tissue of the double-null embryos. Neither of the single-null embryos exhibited any of these phenotypes. These various roles of the three Mam proteins could be due to their differential physical characteristics and/or their spatiotemporal distributions. These results indicate that engagement of Mam is essential for Notch signaling, and that the three Mam isoforms have distinct roles in vivo. © 2011. Published by The Company of Biologists Ltd. |
| Keywords: | signal transduction; controlled study; protein expression; unclassified drug; nonhuman; flow cytometry; polymerase chain reaction; protein domain; animal cell; mouse; mammalia; animals; mice; mus; carboxy terminal sequence; embryonic stem cell; protein protein interaction; cell protein; mice, mutant strains; notch receptor; transcription factor; wild type; mice, inbred c57bl; b lymphocyte; transcription factors; nuclear proteins; in situ hybridization; gene expression regulation, developmental; survival time; blotting, western; dna; heterozygosity; nucleotide sequence; receptors, notch; fibroblast; fibroblasts; plasmids; upregulation; trans-activators; dna primers; luciferases; forebrain; nervous system development; rhombencephalon; mesoderm; growth retardation; neural tube; null allele; organogenesis; spleen cell; metazoa; notch2 receptor; notch3 receptor; notch4 receptor; transcription factor hes 5; branchial arch; haploinsufficiency; gestation period; microtubule associated protein 2; mastermind; notch signaling; real-time polymerase chain reaction; transcription factor mash1; ankyrin; mastermind like 1 protein; mastermind like 3 protein; protein hesr1; protein hesr3; protein lfng; rbp j protein; transcription factor dll1; transcription factor math3; blotting, southern; glycosyltransferases |
| Journal Title: | Development |
| Volume: | 138 |
| Issue: | 23 |
| ISSN: | 0950-1991 |
| Publisher: | Company of Biologists |
| Date Published: | 2011-12-01 |
| Start Page: | 5235 |
| End Page: | 5246 |
| Language: | English |
| DOI: | 10.1242/dev.062802 |
| PROVIDER: | scopus |
| PUBMED: | 22069191 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 December 2011" - "CODEN: DEVPE" - "Source: Scopus" |
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