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Cell Signalling Biology Michael J. Berridge Module 2 Cell Signalling Pathways 2 117

Module 2: Table Notch signalling components
Notch signalling toolkit.
Components Comments
Notch stimuli These Notch stimuli contain an N-terminal DSL (Delta, Serrate and LAG-2)
domain that interacts with the Notch receptor (Module 2: Figure Notch
signalling)
Delta 1
Delta 3
Delta 4
Delta-like-4 (DLL4) Responsible for lateral inhibition during angiogenesis (Module 9: Figure
angiogenesis signalling)
Jagged 1
Jagged 2
Receptors
Notch 1
Notch 2
Notch 3
Notch 4
Notch modulators
Numb A major inhibitor of Notch. It facilitates the endocytic removal of Notch from the
plasma membrane (Module 2: Figure Notch modulation)
Crumbs May function to inhibit γ-secretase activity thereby reducing the activation of
Notch
Proteases
ADAM-10 Also known as Kuzbanian or MADM. Functions in neural and cardiac
development
ADAM-17 Also known as tumour necrosis factor-α (TACE)
Furin A protein convertase that cleaves site 1 (S1) during Notch receptor maturation
γ-secretase An enzyme complex containing presenilin, nicastrin, PEN2 and APH1
Glycosyltransferases
Fringe family A family of glycosyltransferase in the Golgi that glycosylates Notch to alter its
binding affinities to Delta and Jagged
Lunatic fringe
Radical fringe
Manic fringe
Transcriptional regulators
CSL CSL [CBF-1, Su(H), Lag-1] represses Notch target genes (Module 2: Figure
Notch signalling)
MAM Mastermind
SKIP Ski-interacting protein interacts with CSL and the ankyrin repeats of NICD
Notch target genes
HES1 Hairy and enhancer of split 1 (HES1) represses transcription of tissue specific
genes responsible for differentiation
HES2
HES7
HEY1
HEY2
HEYL
ESR
Ubiquitin ligases
Itch A Hect domain E3 ligase that functions in Notch trafficking (Module 2: Figure
Notch modulation)
Deltex A Ring finger E3 ligase that functions in Notch trafficking (Module 2: Figure
Notch modulation)
Mind bomb (Mib) Ring finger E3 ubiquitin ligases that initiate the trafficking of Delta and Jagged
(Module 2: Figure Notch modulation)
Neutralized (Neur) Ring finger E3 ubiquitin ligases that initiate the trafficking of Delta and Jagged
(Module 2: Figure Notch modulation)
SEL10 A nuclear ubiquitin ligase that interacts with the phosphorylated form of NICD
(see Step 8 in Module 2: Figure Notch signalling)

10. Once NICD is removed from the activation com- • Proliferation of satellite cells in skeletal muscle is en-
plex and degraded, the different co-activators fall hanced by Notch signalling (Module 8: Figure Satellite
away and are replaced by the repressors that result cell activation).
in gene repression. Gene repression also depends on • The self renewal of haematopoietic stem cells (HSCs)
the recruitment of histone deacetylase (HDAC) that is facilitated by Notch signalling that acts by inhibiting
deacetylates chromatin further shutting down tran- differentiation (Module 8: Figure HSC regulation).
scriptional activity. • Notch signalling is responsible for the process of lat-
eral inhibition that inhibits tip cell formation during
angiogenesis (see Step 2 in Module 9: Figure angiogen-
esis signalling).
Notch signalling controls a number of developmental
events and continues to have a role during adulthood par- Alterations in Notch signalling have been implicated in a
ticular in maintaining the stem cell population: number of cancers. For example, overexpression of Notch

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