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

REST

RamANK

REST

RamANK

REST

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.

RamANK

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…

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

RamANK

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

RamANK

REST

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.