2. (8pts each) Short response (max 2 sentences each IN YOUR OWN WORDS) A. How ar

Question

2. (8pts each) Short response (max 2 sentences each IN YOUR OWN WORDS) A. How are caspases prevented from signaling the cell for apoptosis until the appropriate time? B. Please provide a specific mechanism that TURNS OFF the following signaling molecules that are commonly found in RTK pathways. Also, please circle which one(s) need to be "turned off" for the signaling response to be stopped Receptor Tyrosine Kinase: Ras-GTPase: MAP Kinase Kinase: Calcium (Ca2) C. Please circle whether the following proteins are proto-oncogenes or tumor suppressors: i. Caspases i. DNA damage checkpoint protein (ex. p53)proto-oncogene tumor suppressor ii G1/S-phase cyclin (ex. Cyclin D) iv. Wee1 proto-oncogene tumor suppressor proto-oncogene / tumor suppressor proto-oncogene tumor suppressor

Explanation / Answer

Question A
The accidental activation of caspases and subsequently cell death by apoptosis is inhibited by the inhibitor-of-apoptosis (IAP) family of proteins. The activation of apoptosis pathway leads to release of mature Smac proteins (N-terminal 55 amino acid residues targeted for the mitochondria are excised) from the mitochondria to cytosol. This relieves IAP inhibition and activates the processed initiator and effector caspases for the apoptosis.

Question B
Receptor Tyrosine Kinase:
Regulation of receptor tyrosine kinase (RTK) is controlled by positive and negative feedback mechanisms. Following mechanisms are involved in shutting off the RTKs.
1. Protein tyrosine phosphatases
The enzyme Protein Tyrosine Phosphatase (PTPs) dephosphorylates the activated phosphorylated tyrosine residues present with the RTKs. Eventually, the signal gets terminated.
2. Herstatin
Herstatin is an inhibitor which binds to RTKs and stops the receptor dimerization and tyrosine phosphorylation.
3. Receptor endocytosis
Clathrin-mediated endocytosis of RTKs leads to the down-regulation of signaling cascade.

Ras-GTPase
GTP is hydrolyzed from Ras-GAP (GTPase-activating protein) complex and regenerates Ras-GDP. GAP binding of Ras increases the reaction rate hundred-fold, therefore inactive Ras-GDP persists and the signal gets terminated.

MAP kinase-kinase
The mitogen-activated protein kinase pathways (MAPKs) are started alongside receptor tyrosine kinases (RTKs). The effectors of MAPKs are stimulated by phosphorylation of threonine and tyrosine residues. The increasing phosphatases and the regulatory proteins inactivate MAP kinase RTK cascades.

Question C
The right choice has been shown in bold font face
Caspases:                    

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