Reactome | DTX binds NOTCH1

DTX binds NOTCH1

Stable Identifier

R-HSA-1980122

Type

Reaction [binding]

Species

Homo sapiens

Compartment

cytosol, plasma membrane

ReviewStatus

5/5

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Deltex (DTX) protein family in mammals includes four proteins: DTX1, DTX2, DTX3 and DTX4. Human DTX1 interacts with cdc10/ankyrin repeats of the intracellular domain of NOTCH1 and NOTCH2, similar to the interaction of Drosophila deltex and notch proteins (Matsuno et al. 1998). Studies on mouse deltex proteins showed that the N-terminal region of Dtx1, homologous to the Drosophila deltex domain I, is necessary and sufficient to bind the ankyrin repeats of Notch. Besides Dtx1, this Notch-interacting region is conserved in Dtx2 and Dtx4. Dtx3 lacks most of the N-terminal sequence homologous to Drosophila deltex domain I and cannot bind ankyrin repeats of mouse Notch1, while Dtx1, Dtx2 and Dtx4 bind to it strongly. Dtx3 also has a different class of RING finger domain than the other three deltex proteins (Kishi et al. 2001). While deltex colocalizes with Notch at the plasma membrane and in the cytosol, there is no colocalization between NICD and deltex in the nucleus, suggesting that DTX does not mediate NOTCH signaling by direct interaction with nuclear NICD (Matsuno et al. 1998). Recent studies in Drosophila indicate that Deltex, acting as an E3 ubiquitin ligase, may activate ligand independent Notch proteolysis and signaling by shunting Notch into an endocytic pathway that involves HOPS and AP-3 complexes (Wiklin et al. 2008).

Literature References

PubMed ID	Title	Journal	Year
11226752	Murine homologs of deltex define a novel gene family involved in vertebrate Notch signaling and neurogenesis Kishi, N, Tang, Z, Maeda, Y, Hirai, A, Mo, R, Ito, M, Suzuki, S, Nakao, K, Kinoshita, T, Kadesch, T, Hui, C, Artavanis-Tsakonas, S, Okano, H, Matsuno, K	Int J Dev Neurosci	2001
19000840	Drosophila HOPS and AP-3 complex genes are required for a Deltex-regulated activation of notch in the endosomal trafficking pathway Wilkin, M, Tongngok, P, Gensch, N, Clemence, S, Motoki, M, Yamada, K, Hori, K, Taniguchi-Kanai, M, Franklin, E, Matsuno, K, Baron, M	Dev Cell	2008
9590294	Human deltex is a conserved regulator of Notch signalling Matsuno, K, Eastman, D, Mitsiades, T, Quinn, AM, Carcanciu, ML, Ordentlich, P, Kadesch, T, Artavanis-Tsakonas, S	Nat Genet	1998