The accidental discovery of p53 tumour suppressor protein

When we talk about cancer the immediate response of a layman person is something which is not curable, but after so many years of cancer biology research, scientists have found out that any type of cancer can be cured depending on the stage of cancer. Over the period, researchers have also found many genes and proteins, which are involved in causing cancer and also preventing cancer. In this report, we will have a brief understanding of the accidental discovery of p53 tumour suppressor protein.

What is p53 protein?

A p53 protein is coded from a tumour suppressor gene whose function is to stop the formation of tumours. In cell p53 protein binds to DNA which activates a gene producing p21 and when p21 forms a complex with cell division protein cdk2 it stops the process of cell division and so when p53 protein is mutant the p21 protein is not produced leading to a lack of signal for cell division and thus the cell divides uncontrollably to form tumour.

When was the first time p53 protein discovered?

In 1979 a group of researchers was working on chemically induced mouse sarcoma and when antiserum was produced against the tumour antigens and later immunoprecipitated, they found a different protein which was only observed in transformed cells

Another group of researchers was working in the same year and they found that when a simian vacuolating virus (SV40) was coimmunoprecipitated with antibodies generated against the viral protein a new protein was coimmunoprecipitated because of the interaction of the protein with the T antigen of the SV40 virus. Thus at the same time, both the groups of researchers came to know about a protein that is now known as p53.

What experiments let to the discovery of p53?

Though there were six groups of researchers each working independently, reported the discovery of p53 protein in the same year. In this report we will mainly focus on the literature Deleo et al. 1979 which was working on detection of a transformation-related antigen in chemically induced sarcomas and other transformed cells of the mouse.

What they did was they took  BALB/c mouse laboratory strain and induced mouse sarcoma by treating them with polycyclic hydrocarbons such as methylcholanthrene, in order to know the tumour antigens associated with the tumour formation. As tumour antigen produces an immune response, when we are able to know the specific tumour antigen associated with a particular tumour formation induced by certain compounds, it can be used to attain immunization by using irradiated tumour antigens or cells. So they knew serological identification of these antigens would clearly facilitate the analysis of different tumours.

After inducing mouse sarcoma when they tried to immunoprecipitate [35S] methionine-labeled sarcoma cell extracts with antisera recognizing the methylcholanthrene induced antigens they detected a crossreacting antigen and later they found that this antigen(p53) is only present in transformed cells.

• Antiserum– blood serum containing antibodies against specific antigens against specific diseases.
• Tumour-specific antigens- antigens that are only found in tumour cells and induce an immune response.
• Cross-reactivity- when two antigens have similar structural regions that the antibody recognizes and thus the cross-reactivity between antigens occur.

Why p53 is not found in non transformed cells?

The p53 protein is not found in non transformed cells because it is degraded by a E3 ligase (MDM2). When there are diverse stress stimuli that lead to activation of oncogenes different cell signalling pathways help in the rise of p53 because of the inhibition of the MDM2.

Conclusion

Today after 41 years of discovery of p53 protein it led to many facts about this protein from thinking it to be an oncogene to knowing it is actually a tumour suppressor protein. There are still many researches going on about this protein to understand the different mechanism and how it can be used to treat cancer.

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