What are the most common mutations associated with the p53 tumor suppressor gene

Question

What are the most common mutations associated with the p53 tumor suppressor gene that are implicated in many human cancers?

A. Dominant negative mutations in p53 eliminate MDM2 binding and tetramerization.

B. Dominant negative mutations in p53 eliminate DNA binding and/or reduce its stability.

C. Dominant gain-of-function mutations in p53 enhance DNA binding and increase its stability.

D. Recessive loss-of-function mutations in p53 eliminate DNA binding and/or reduce its stability.

E. Recessive loss-of-function mutations in p53 eliminate MDM2 binding and tetramerization.

Explanation / Answer

p53 is a tumor suppressor gene, and is a transcription factor. It has four identical subunits, which form a dimer or dimer, that is, they form a tetramer. Mutations associated with this gene have several implications. The most common among them is found to be an N-delta mutation which interferes with the wild type p53 and inhibits its function. Such an interference is called dominant-negative mutation. The defective protein cannot bind DNA efficiently. Further, mutant p53 were found to inactivate the transactivation of MDM2 binding. However, formation of tetramers is not affected. To inactivate MDM2 binding, there shall be at least three mutant proteins per tetramer.

Hence, the correct answer is B. Dominant negative mutations in p53 eliminate DNA binding and/or reduce its stabilty.

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