Notch signaling

BACKGROUND TO NOTCH SIGNALING

[Wikipedia]

PMID 12651094

Pre-pathway events

• Maturation of the notch receptor involves cleavage at the prospective extracellular side during intracellular trafficking in the Golgi complex.
• This results in a bipartite protein, composed of a large extracellular domain linked to the smaller transmembrane and intracellular domain (NICD).

Pathway events

• Binding of ligand promotes two proteolytic processing events; as a result of proteolysis, the intracellular domain is liberated and can enter the nucleus to engage other DNA-binding proteins and regulate gene expression.

PROBLEM

Both Susan and Peter D'E have queried the Notch signaling terms.

• Where does the Notch signaling pathway end, given that it's such a short pathway.

• Are the co-activators/repressors that regulate transcription with Notch PART OF the pathway, or do they regulate the pathway?

• What do we mean by 'positive regulation of transcription of Notch receptor target GO:0007221' ?

[Term]
id: GO:0007221 
name: positive regulation of transcription of Notch receptor target
namespace: biological_process
def: "The activation of transcription of specific genes as a result of Notch signaling, mediated by the Notch intracellular domain." [PMID:12651094]
synonym: "N receptor target transcription factor activation" RELATED []
synonym: "Notch receptor target transcription factor activation" RELATED []
is_a: GO:0045944 ! positive regulation of transcription from RNA polymerase II promoter
relationship: part_of GO:0007219 ! Notch signaling pathway

• Annotations to GO:0007221 are mainly to:
  • Notch
  • RBPJ (part of the transcriptional activation complex that binds NICD to promote transcription of target genes).

• The whole pathway (ligand->Notch->nuclear TF/cofactors) is involved in regulation of transcription so having this term as part of the pathway is misleading. I believe the term is meant to represent the nuclear events that up-regulate transcription of target genes.

PROPOSAL

• We could rename GO:0007221 so that it points to nuclear events (occurs_in: nucleus)
• Or divide it up into the functions of the individual GPs.

E.g.
RNA polymerase II transcription factor binding transcription factor activity involved in Notch signaling pathway
--[isa]RNA polymerase II transcription coactivator activity involved in Notch signaling pathway
sequence-specific DNA binding RNA polymerase II transcription factor activity involved in Notch signaling pathway