The notch protein is part of the greater picture, the notch signaling pathway. The actual protein serves as a trigger straddling the inside and outside of the cell membrane. When certain proteins bind to the exterior of the notch, the interior releases other proteins which make their way to the cell nucleus to alter gene expression. Some responsibilities delegated to the notch include but are not limited to cell proliferation, cell differentiation, and apoptosis.
Notch proteins are not an universal brand of amino acids, rather they are only found in Metazoans, or animals. Within these creatures, the variety of notch proteins range from notch-1 to notch-4. These notches correspond with five ligands termed Jagged 1, Jagged 2, Delta -1, Delta -2, Delta -3. When cancer or other diseases strike, the notch complex is usually deactivated, leading to a weak T-Cell response.
Typically, Notch is triggered primarily though direct contact, meaning that the external proteins must physically bind them to the exterior. Moreover, each individual cell that makes contact with the notch alters a different gene expression, so the process is very localized and specialized. For example, a particular cell would have to bind to the notch for a signal to activate apoptosis.
What is GSI?
GSI is a man-made pharmacological agent known to block notch activation. It works by inhibiting γ-secretase, an enzyme that cuts off the ends of proteins. Some viruses, like as HIV, must cleave proteins to function properly. With GSI, the HIV retrovirus is effectively prevented from reproducing, thereby halting the progression of the disease.
How GSI Inhibits KS
GSI inhibits the γ-secretase enzyme, which in turn prevents notch signals from reaching KS. Witho...
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Nude Mouse Model
Several mice were injected with SLK cells and were observed for 4-6 weeks. The mice tumors that had resulted were then directly injected with GSI while some were left untreated as controls. The animals were eventually killed from the tumors and their tumors were observed over time. It was discovered that the continuous injections of GSI caused pain for the animals. The pain was a minor problem that was solved by giving another dose of a chemical called buprenorphine (amount of 0.1mg/kg) helping the pain slowly go away. Even with the new chemical added, the results did not vary in any extreme manner.
Work Cited
Curry, C.L., Reed, L.L., Golde, T.E., Miele, L., Nickoloff, B.J., Foreman, K.E., 2005. Gamma Secretase Inhibitor blocks Notch Activation and induces apotosis in Kaposi's Sarcoma tumor cells. Oncogene 24, 6333-6344.