Happy Friday Everyone!
Welcome back to those of you who have read my blogs before, and to those of you who are joining me in Week 5, greetings! In last week’s blog, I described my ongoing research with the tumor suppressor protein, p53. This week’s blog will be a continuation of last week’s, so I recommend reading last week’s blog if you haven’t yet.
So if we go back 168 hours, how many of you can recall the main difference between wild-type p53 and mutant-type p53? Simply put, wild-type p53 prevents cancer by repairing or killing cells facing some sort of DNA damage. On the other hand, mutant p53 promotes cell division and impairs the function of wild-type p53. If there was anyone who remembered that, kudos to you! For those who didn’t, I’m disappointed … I’m just kidding.
Covering the basics of p53 last week, I will go more into the complexities behind p53 in this week’s blog. I will begin with discussing characteristics of p53. p53 is a nuclear transcription factor, meaning that it controls the transcription of DNA and determines whether certain genes will get expressed. In other words, if the p53 transcription factor is not present, the gene for apoptosis may not get expressed. At the same time, p53 is a Knudson-type tumor suppressor meaning that both alleles must be inactivated to cause some sort of phenotypic change.
As a majority of us have learned in biology, the function of a biological substance is dependent on its structure. Observing the structure of p53, the protein has four main domains:
- NH2– terminal transactivation domain
- DNA binding domain: where p53 binds with p53-responsive element on DNA
- COOH– terminal oligomerization domain: forms homo-tetrameter
- Proline-rich domain: associated with pro-apoptotic functions
Below is my diagram of p53’s structural domains:
The reason I am discussing the structure of p53 is because structural differences are what account for differences between wild-type and mutant p53. For example, mutant p53 will have a deleted pro-rich domain which results in the loss of the protein’s apoptotic functions. Also contributing to the functions of mutant p53 are two nuclear signals:
- Importin alpha : enables the nuclear localization of p53 (REMEMBER, p53 is a nuclear transcription factor and must remain in the nucleus
- CRM1: allows the nuclear export of p53
In mutant p53, the COOH-terminal is disrupted resulting in deranged tetrameter formation that enables the binding of CRM1 that brings p53 out of the nucleus, preventing the transcription of genes that would either repair damaged DNA or enable apoptosis of blemished cells.
As this blog is probably getting too long for a majority of readers, I will stop here. In the coming weeks, I will post a blog regarding p53’s involvement in cancer treatment. In addition, due to certain complications in the lab, I was unable to attend the lab this week to continue restriction DNA digestion. I promise to provide updates in the coming weeks. In the blogs to come, I will be making connections between lab work and independent research in order to discuss the development of my final product: a research paper!
As always, thanks for reading. Stay tuned for next week. Cheers!