By Kelsey Godfrey and Pritha ShahBIOL 391-001
13 October 2011
Notch
Notch
Notch
Notch
RamANK
REST RamANK
REST RamANK
REST
RamANK
REST
The Delta and Notch proteins connect.
This triggers ADAM and γ-secretase to cleave the Notch protein.
RamANK
REST
RamANK
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RamANK
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Receiving Cell
Signaling Cell
Once cleaved, the Delta-Notch portion is taken into the signaling cell via endocytosis and degraded.
Delta
Notch
Notch
Delta
Notch
Delta
Notch
Delta
Meanwhile, the NICD (or Notch Intracellular Domain) makes its way into the nucleus and interacts in four possible ways.
NICD
Possibility #1: This targets genes for the remodeling of chromatin.
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SKIP
CSL
HATs
SKIP, also known as SNW1, is used for protein binding.
HATs (Histone Acetyltransferase 1) controls transferase activity.
CSL (aka RBPJ or CBF1) is the recombination signal binding protein for immunoglobulin kappa J region.
Just changing one gene, can change the entire funtion, which leads to possibility #2…
Possibility #2:Switching HATs, which deals with transferase activity to SMRT/HDACs (dealing with hydrolase activity) changes this target gene’s purpose.
SMRT/HDACs is histone deacetylase 1, which deals with hydrolase activity.
CSL
CSL
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REST
Possibility #3: Another CSL (or RBPJ) can be added. This is involved in the transcription of the gene Hairy/E(spl), which will positively regulate cell proliferation.
CSL
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Possibility #4: This is another way genes can be targeted for chromatin remodeling.
MAML
MAML, also known as mastermind, is involved in protein binding.
This video can also be viewed here: Delta-Notch Signaling Pathway
Gilbert, S. F. (2006). Developmental Biology (Eighth ed., pp. 160-161). Sunderland, MA: Sinauer Associates, Inc.
Humanpath.com. (October 10, 2011). Notch Signaling Pathway.
In HumanPath.com: A Website Dedicated to Human Pathology. Retrieved October 10, 2011, from
http://www.humpath.com/spip.php?article289. Qiagen. (October 10, 2011). GeneGlobe Pathways. In Qiagen -
Sample & Assay Technologies. Retrieved October 10, 2011, from
https://www.qiagen.com/geneglobe/pathwayview.aspx ?pathwayID=325.
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