Question

Please answer all

1. The loss of Smad4 coupled with the loss of PTEN is not common in human cancers because both mutations lead to suppression of TGF- signals. A) True B) False

2. Tumor-promoting phorbol esters such as TPA mimic the lipid second messenger diacylglycerol. The tumor promoting effects are most likely due to the suppression of TGF signals. A) True B) False

3. EGF signals are enhanced by proton pumps that reduce the pH in endosomes carrying the endocytosed EGF receptor. A) True B) False

4. While it is widely believed that the GTPase Rheb directly activates mTORC1, the ability of PA (18:1-16:0) to activate mTORC1 in the absence of Rheb strongly suggests that it is the ability of Rheb to activate PLD that is the last step in the activation mTORC1. A) True B) False

5. PLC converts PIP2 (phosphatidylinositol-4,5-bis phosphate) to DG (diacylglycerol) and IP3 (inositol-1,4,5-trisphosphate), leading to inhibition of PLD (phospholipase D). A) True B) False

Answer 1

1. True

Explanation –

The central mediator of TGF-β signaling is SMAD4 and in general remains inactivated over varying degrees of different types of cancers. Only loss of SMADA4 does not initiates tumor formation but loss of SMADA4 initiate the tumor progression through other genes such as KRAS etc. Now as we understand both SMAD4 and PTEN regulate each other’s function through a negative feedback loop. Thus, if one is deleted the other one compensates for its loss. But deletion of both together is no a common scenario.

2. True

Explanation-

Phorbol esters do mimic the action of the lipid second messenger diacylglycerol (DAG) and hence bind with high affinity to the cPKCs and nPCKS. This binding of DAG to c,n PCKs stimulate the receptors that leads to DAG generation. Tumor promoting phorbol esters induces TGF-b regulation and leads to downregulation of PKC-a and suppression

3. False

Explanation –

The EGF receptor signaling interact with vacuolar H+-ATPase and inhibits the proton pump, thereby causing alkalinization of endosomes and recycling of endosomes and the receptor.

4. True

Explanation –

mTORC1 is made up of mTOR, Raptor, mLST8, PRAS40, and DEPTOR and its activation depends on the Rag and Rheb GTPases and also depends on the signals from oxygen, energy molecule (such as ATP), glucose etc. and growth factors. Alternatively, Rheb can activate mTORC1 wi

has been proposed to indirectly activate mTORC1 by acutely stimulating phospholipase D1 (PLD1)