Chapter C, Problem 1P

C.1Identify the normal functions of the genes whose mutations are associated with development of cancer.

RBI(retinoblastoma)

c $\text{-}$ MYC(Burkitt’s lymphoma)

p $53$(Li $\text{-}$ Fraumeni syndrome)

APC(familial adenomatous polyposis)

Which of these genes would you classify as a protooncogene and which as a tumor suppressor gene? Explain your categorization for each gene.

Summary Introduction

To review:

To identify normal function of the given genes, as the mutation of these genes is related to cancer development.

The normal function of $\text{RB1}$ gene is to be identified.

The normal function of $\text{c-MYC}$ gene is to be identified.

The normal function of ${\text{p}}^{\text{53}}$ gene is to be identified.

The normal function of APC is to be identified.

The proto-oncogene and tumor suppressor genes is to be classified.

Introduction:

Proto oncogenes are those which perform normal function in the cell cycle. Mutation in proto oncogenes results in over expression of proto oncogenes which leads to uncontrolled cell division, now, they are termed as oncogenes. On the other hand, genes normally faction in DNA damage repair and control the normal cell cycle. If mutation occurs in this gene, they lose their function and DNA damage cannot be repaired; in such condition, the cell is termed as transformed, and it undergoes uncontrolled cell division.

These genes prevent cell transformation and maintain a normal cell cycle and are termed as tumor suppresser genes.

Explanation of Solution

RB1 normally inhibit the ${\text{E}}_{\text{2}}\text{f}\text{. E2F}$ is the transcription factor of S-phase cyclin (cyclin D). Thus, the cell cycle is arrested. If $\text{RB1}$ is mutated, it cannot inhibit ${\text{E}}_{\text{2}}\text{F}$, and free ${\text{E}}_{\text{2}}\text{F}$ facilitates the continuous expression of s-phase cyclin, which results in continuous cell proliferation.

$\text{C-MYC}$ performs multiple functions and acts as a transcription factor of protein that plays a role in cell division. In some conditions, it acts as transcription factor for protein that plays a role in cell cycle arrest. Mutation in $\text{C\_MYC}$ results in overexpression which facilitates rapid and continuous proliferation. Overexpression of $\text{C\_MYC}$ is mostly due to its translocation from one chromosome to another.

${\text{P}}^{\text{53}}$ is also known as guardian of genome. It is a tumor suppresser gene. The function of ${\text{P}}^{\text{53}}$ ^is is that it plays an important role in DNA damage check point and initiates repair mechanism in case of DNA damage. It acts as a transcription factor of ${\text{P}}^{\text{21}}$, which inhibits $\text{G1}$ and S phase $\text{cyclin-CDK}$ complex.

APC (Adenomatous polyposis coli) functions as a tumor suppresser gene. It is involved in proteolytic cleavage and degradation of $\text{β-catenin}$. $\text{β-catenin}$ functions as a transcription reason of several genes. If loss of function mutation occurs in APC, it cannot inhibit $\text{β-catenin}$ and expression of genes will be expressed in continuous manner.

$\text{C-MYC}$ will be classified as proto oncogenes as it is involved in the progression of cell division and inhibits apoptosis. $\text{RB1}$, $\text{p53}$, and APC are classified as tumor suppressor genes; these arrest the cell cycle and induce apoptosis in irreversible DNA damage condition.

Conclusion

Proto oncogenes accelerate rate of normal cell division and are responsible for the formation of tumors. Tumor suppresser genes suppress the formation of tumor.