Intrinsic activity of the Lin-12 and Notch intracellular domains in vivo

Howard Hughes Medical Institute, Department of Genetics and Development, Columbia University College of Physicians and Surgeons, New York, New York 10032.
Cell (Impact Factor: 32.24). 08/1993; 74(2):331-45. DOI: 10.1016/0092-8674(93)90424-O
Source: PubMed


The lin-12 gene of C. elegans and the Notch gene of D. melanogaster encode structurally related transmembrane proteins that mediate intercellular signaling. We show that truncated forms of these proteins consisting of only the intracellular domains cause cell fate transformations associated with constitutive activity in their respective organisms. This activity does not depend on endogenous gene function. Our results indicate that the intracellular domains of Lin-12 and Notch have intrinsic activity and that the principal role of the extracellular domains in the intact proteins is to regulate this activity. Our results also suggest that equivalent truncated forms of lin-12/Notch family members in vertebrates, including known oncogenes, are similarly active.

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    • "The canonical Notch signaling involves ligand-dependent processing, release, and translocation into the nucleus of the Notch intracellular domain (Nintra/NICD) to activate target genes [31]–[33]. Up-regulation of canonical Notch signaling is associated with the development of the anti-neurogenic phenotype [34]–[36]. The heph embryos manifest the anti-neurogenic phenotype due to increased canonical Notch signaling [22]. "
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    PLoS ONE 07/2014; 9(7):e98585. DOI:10.1371/journal.pone.0098585 · 3.23 Impact Factor
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    • "The same procedure was used for flies expressing GAL4/UAS combinations to knockdown genes using RNAi or to express reporter lines. The following Drosophila stocks were used: Gbe-Su(H)-lacZ (NRE-lacZ) (Furriols and Bray, 2001), Gbe-Su(H)-Gal4 (NRE-Gal4) (Zeng et al., 2010), FRT82B dakt 1 (Rintelen et al., 2001), FRT82B inr 31 (Brogiolo et al., 2001), UAS-dinr RNAi RII2 (a gift from R. Ueda, NIG, Mishima, Japan), UAS-N icd (Struhl et al., 1993), UAS hFOXO3a-TM (Jünger et al., 2003), FRT82B dp110 1C1 [obtained from Hugo Stocker (Willecke et al., 2011)], UAS cut 5 (Krupp et al., 2005), foxo Δ94 and FRT82B foxo Δ94 (Slack et al., 2011), FRT82B inr ex15 (Song et al., 2003) and string-lacZ ( p[w+ stgB R6.4]) (a gift from B. Edgar, ZMBH, Heidelberg). Tub-gal80 ts , UAS-rpr, UAS-dinr del , UAS-cut RNAi TRIP29625, UAS-N RNAi TRIP28981, UAS-p60(PI3K DN ), fizzy related-lacZ and FRT82B strains were from the Bloomington Stock Center. "
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    Journal of Cell Science 07/2014; 141(15). DOI:10.1242/dev.108399 · 5.43 Impact Factor
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    • "The first, NICD, consists of the intracellular domain only, being truncated just C-terminal to the transmembrane domain. The resulting protein is nuclear and its activity is independent of γ-secretase activity [93–95]. The second, NΔECD, retains the transmembrane region and resembles the product of the Kuz/Adam10 activating cleavage [93,96]. "
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    Methods 04/2014; 68(1). DOI:10.1016/j.ymeth.2014.03.029 · 3.65 Impact Factor
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