Question

Conditional alleles allow for mutants to have wild type function in one condition and mutant function in another condition. Temperature-sensitive alleles are one example of conditional alleles that are commonly used. At the permissive temperature, the gene has normal function, whereas at the restrictive temperature, the gene has mutant function. You are studying the Ras signaling pathway and you obtain a temperature-sensitive Ras mutant. At the permissive temperature, Ras functions normally. At the restrictive temperature, Ras is permanently in the GTP-bound state. Would you expect cells to continue growing or stop dividing when at the restrictive temperature? Explain your answer.

Answer 1

Temperature sensitive alleles are an example of conditional alleles that are commonly used. At the permissive temperature, the gene has normal function, whereas at the restrictive temperature, the gene has mutant function. Ras proteins functions as molecular binary switches that act back and forth between its active and inactive state as 'on' and 'off' states during signal transduction. It cycle between the GDP and GTP bound states. When Ras protein remains bound to GTP it is in active state whereas when bound to GDP it remain in inactive state. It helps in signal transduction of cell growth and differentiation. In normal process of signal transduction Ras functions in its GTP binding form. The conversion of stable inactive GDP-bound forms to the active GTP-bound form is stimulated by guanine nucleotide exchange factors (GEFs) and conversion back to the inactive GDP-bound form is mediated by GTPase activating proteins (GAPs).

At permissive temperature, Ras functions normally where it remains bound to its GTP active form and transmit signal downstream resulting in cell growth and division by regulating transcription of genes. So under normal condition it exhibit wild type function at permissive temperature by promoting cell growth. But at restrictive temperature, Ras protein remain permanently in the GTP-bound state as it become mutant, causing abnormal cell growth and proliferation thereby leading to cancer. Mutation in the proto-oncogene of Ras protein at restrictive temperature lead to permanent transition of Ras protein into its active GTP-bound state and never returns to its inactive GDP-bound state. Hence, it constantly floods the cell giving them the signal to undergo cell division even in the absence of growth factor signals.

Therefore, the cells will continue to grow at the restrictive temperature.