Question

1. What will happen under scenario a to d? Provide explanation for your answer.
   1. Ras with enhanced GAP (GTPase Activating Proteins) activity

2. A gain-in-function mutation in Bcl2

3. A mutant RTK lacking cytosolic tail containing tyrosine sites

4. Loss-in-function mutation in a phosphatase for p21

Answer 1

1) GTPase Activating protein:

Ras belongs to the GAP1, a subfamily of Ras GTPase-activating protein with dual RasGAP specificity is epigenetically silenced in several tumor types. Ras is a GTP-binding protein. Two characters of Ras proteins are an inactive GDP-bound and an active GTP bound state. And these characters are controlled by Ras guanine nucleotide exchange factors/GEFs and Ras GTPase-activating protein(GAPs). Ras GAP enhances the intrinsic activation of Ras GTPase activity and this leads to the inactivation of Ras through GTP into GDP conversion, whereas Ras GEFs trigger activation of Ras by increasing the exchange of GDP for GTP. The membrane recruitment of s regulated by interaction with calcium and lipids. In 20-30% of humans, oncogenic Ras mutants are incapable of hydrolyzing GTP. The post-translational modification or mutations of RasGAPs leads to the inactivation or deregulation of the proteins and also takes place in tumor formation in cells containing wild-type Ras.

2)A gain-of-function mutation in BCL2:

The genetically controlled cell death is an Apoptosis, that is required for normal development and tissue homeostasis. The survival of cells depends on the maintenance of mitochondrial integrity controlled by a well- balanced interplay between anti and pro-apoptotic B cell lymphoma 2 family members, which is popularly known as BCL2. Within BCL2 family, BH3-only proteins like Bim, Puma or Bid act as sentinels which are activated in response to a broad range of development/environmental cues to trigger mitochondrial apoptosis. They are able to do this by neutralizing anti-apoptotic BCL2 proteins and by directly activating the high redundant but rate-limiting cell death effectors Bax and Bak. And if once activated, these forms homodimers that then assembles or arrange into higher-order oligomers enabling activation of the protease of the Casp family and the cell death. Their gene is critical for FL pathogens. The high-level expression of BCL2 was confirmed in numerous human tumors sparking extensive gain and loss of function studies in different model systems.

3) RTKs:

RTKs- Receptor tyrosine kinases is one a class of transmembrane receptor and are characterized by the intrinsic tyrosine kinase activity of their cytoplasmic regions. RTKs play a critical role in regulating survival, metabolism, migration, cell differentiation, and proliferation. This is expressed in tissues throughout the body both during immaturity and adulthood. Among all, a few RTK cytosolic regulators largely kinases which are responsible for deciphering incoming signals associated with RTK activation and the interpretation from such signals trigger divers output that shapes the cellular response. Chimeric fusion protein leads with the help of chromosomal rearrangement of RTKs  

4) Loss-of-function in phosphatase for p21:

We will discuss the molecular mechanism behind a cancer-derived loss of function mutation in the PP2A B56¥ regulatory subunit gene. The highly studied and important tumor suppressor protein is a p53 protein that functions primarily as a transcription factor. Protein phosphatase 2A is a family of serine/threonine phosphoproteins phosphatase that has been implicated as a potential tumor suppressor. Its role in the control of tumor progression is composed to be governed by a small subset of specific B subunits directing PP2A to dephosphorylate and regulate key tumor suppressor or oncogene. The effect of these mutations is the loss of interaction with B56 subunit family members.