Reactome | NOTCH precursor cleaved to form mature NOTCH

NOTCH precursor cleaved to form mature NOTCH

Stable Identifier

R-HSA-1912369

Type

Reaction [transition]

Species

Homo sapiens

Compartment

Golgi membrane

ReviewStatus

5/5

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NOTCH precursor cleaved to form mature NOTCH

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The NOTCH receptor is synthesized as a precursor polypeptide (approx. 300 kDa) associated with the endoplasmic reticulum membrane. The mature NOTCH receptor is produced by proteolytic cleavage to form a heterodimer. The enzyme responsible is a furin-like convertase which cleaves the full-length precursor into a transmembrane fragment (NTM) of approximate size 110 kDa and an extracellular fragment (NEC) of approximate size 180 kDa. The mature NOTCH receptor is reassembled as a heterodimer (Blaumueller et al. 1997, Logeat et al. 1998). Both disulfide bonds and calcium-mediated ionic interactions stabilize the heterodimer (Rand et al. 2000, Gordon et al. 2009). This process takes place in the trans-Golgi network . Mammalian NOTCH is predominantly presented as a heterodimer on the cell surface. Although FURIN-mediated cleavage is evolutionarily conserved, it may not be mandatory for Drosophila Notch function (Kidd et al. 2002).

Literature References

PubMed ID	Title	Journal	Year
9653148	The Notch1 receptor is cleaved constitutively by a furin-like convertase Logeat, F, LeBail, O, Jarriault, S, Seidah, NG	Proc Natl Acad Sci U S A	1998
19701457	Effects of S1 cleavage on the structure, surface export, and signaling activity of human Notch1 and Notch2 Gordon, WR, Vardar-Ulu, D, L'Heureux, S, Ashworth, T, Malecki, MJ, Sanchez-Irizarry, C, McArthur, DG, Histen, G, Mitchell, JL, Aster, JC, Blacklow, SC	PLoS One	2009
12049766	Furin cleavage is not a requirement for Drosophila Notch function Kidd, S, Lieber, T	Mech Dev	2002
9727485	Roles for proteolysis and trafficking in notch maturation and signal transduction Chan, YM, Jan, YN	Cell	1998
10669757	Calcium depletion dissociates and activates heterodimeric notch receptors Rand, MD, Grimm, LM, Artavanis-Tsakonas, S, Patriub, V, Blacklow, SC, Sklar, J	Mol Cell Biol	2000
9244302	Intracellular cleavage of Notch leads to a heterodimeric receptor on the plasma membrane Blaumueller, CM, Qi, H, Zagouras, P, Artavanis-Tsakonas, S	Cell	1997