1. By Kelsey Godfrey and Pritha Shah BIOL 391-001 13 October 2011

2. Delta Delta Delta Delta Notch Notch Notch Notch Ram ANK REST Ram ANK REST Ram ANK REST Ram ANK REST γ -Secretase γ -Secretase γ -Secretase γ -Secretase ADAM ADAM ADAM ADAM The Delta and Notch proteins connect. This triggers ADAM and γ -secretase to cleave the Notch protein.

3. Receiving Cell Signaling Cell Ram ANK REST Ram ANK REST Ram ANK REST Ram ANK REST 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

4. Possibility #1: This targets genes for the remodeling of chromatin. Ram ANK REST 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… SMRT/ HDACs 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.

5. CSL CSL Ram ANK 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.

6. MAML CSL Ram ANK REST Possibility #4: This is another way genes can be targeted for chromatin remodeling. MAML , also known as mastermind, is involved in protein binding.

7. This video can also be viewed here: Delta-Notch Signaling Pathway

8. 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.