29. Cellular level of tumour suppressor protein p53 is maintained by the ubiquitin ligase protein, Mdm2. Over expression of Mdm2 was found to convert a normal cell into cancer cells by
destabilizing p53 .Another protein p19^ARF inhibits the activity of Mdm2 thus stabilizing p53. Loss of p19^ARF function also converts normal cells into cancer cells. Based on the above information, which one of the following statements is correct?
(1) Both MDM2 and p19^ARF are oncogenes.
(2) Both MDM2 and p19^ARF are tumour suppressor genes.
(3) MDM2 is an oncogene and p19^ARF is tumour suppressor gene.
(4) p19^ARF is oncogenes and MDM2 is a tumour suppressor gene.

The correct statement is:

(3) MDM2 is an oncogene and p19ARF is a tumor suppressor gene.

Explanation

• MDM2 is classified as an oncogene because it negatively regulates the tumor suppressor p53 by targeting it for ubiquitin-mediated degradation. Overexpression of MDM2 destabilizes p53, reducing its tumor suppressor functions and thereby promoting cancer development.​

• p19ARF functions as a tumor suppressor gene because it inhibits MDM2 activity, leading to stabilization and activation of p53. Loss of p19ARF results in unchecked MDM2 activity, decreased p53 stability, and increased susceptibility to tumorigenesis.​

This regulatory axis between MDM2 and p19ARF is critical in controlling p53 levels and function in cells, impacting cancer progression.