Why is p53 called p53? π€
A 𧡠about the history and discovery of the most studied gene in human history, also known as the guardian of the genome. 𧬠#pathtwitter #pathX #molecular #history
A 𧡠about the history and discovery of the most studied gene in human history, also known as the guardian of the genome. 𧬠#pathtwitter #pathX #molecular #history
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In the 1970s, David Lane & Arnie Levine started studying a virus called SV40. Their interest was in a viral gene responsible for transformation, the SV40 oncogene called large T antigen. π¦
In the 1970s, David Lane & Arnie Levine started studying a virus called SV40. Their interest was in a viral gene responsible for transformation, the SV40 oncogene called large T antigen. π¦
π§΅2/
Lane's task was to extract the large T antigen protein from cells infected with SV40. He used electrophoresis to separate the protein molecules based on size and charge. β‘οΈ
Lane's task was to extract the large T antigen protein from cells infected with SV40. He used electrophoresis to separate the protein molecules based on size and charge. β‘οΈ
π§΅3/
Whenever he ran electrophoresis to purify the large T antigen, he always found an unknown protein with a molecular weight of 53 kilodaltons. Initially, others in Lane's lab thought it was a contaminant or a breakdown product of the large T antigen. βοΈ
Whenever he ran electrophoresis to purify the large T antigen, he always found an unknown protein with a molecular weight of 53 kilodaltons. Initially, others in Lane's lab thought it was a contaminant or a breakdown product of the large T antigen. βοΈ
π§΅4/
As reports of this protein came from other labs too, it was named p53 based on its molecular weight. β¨
As reports of this protein came from other labs too, it was named p53 based on its molecular weight. β¨
π§΅5/
In 1979, immunological studies identified the p53 protein due to its immunoreactivity with tumor antisera, suggesting its role as a tumor-associated antigen.
Everyone was convinced they had found a new oncogene. The excitement was high! π #Oncogene
In 1979, immunological studies identified the p53 protein due to its immunoreactivity with tumor antisera, suggesting its role as a tumor-associated antigen.
Everyone was convinced they had found a new oncogene. The excitement was high! π #Oncogene
π§΅6/
Wait a minuteβdid I say oncogene? p53 is actually a tumor suppressor gene! This is my favorite plot-twist of the p53 story: its mischaracterization as an oncogene. π§¬
Wait a minuteβdid I say oncogene? p53 is actually a tumor suppressor gene! This is my favorite plot-twist of the p53 story: its mischaracterization as an oncogene. π§¬
π§΅8/
As mentioned above, p53 was initially found bound to the major oncogenic protein of SV40, so it was understandable at the time to think it must be an oncogene as well.
However, some experimental observations did not fit well with the idea that p53 was an oncogene. π§¬#p53
As mentioned above, p53 was initially found bound to the major oncogenic protein of SV40, so it was understandable at the time to think it must be an oncogene as well.
However, some experimental observations did not fit well with the idea that p53 was an oncogene. π§¬#p53
π§΅9/
In 1986, the first tumor suppressor gene, Retinoblastoma gene (RB1), was discovered, confirming Knudson's Two-Hit hypothesis. #rb1
In 1986, the first tumor suppressor gene, Retinoblastoma gene (RB1), was discovered, confirming Knudson's Two-Hit hypothesis. #rb1
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In 1989, this two-hit model was applied to p53, specifically in colorectal tumors. It fit this model, as in virtually all cases, both copies of p53 were mutated. π§¬
In 1989, this two-hit model was applied to p53, specifically in colorectal tumors. It fit this model, as in virtually all cases, both copies of p53 were mutated. π§¬
π§΅11/
This conclusion was confirmed by subsequent findings that patients with inherited mutations of p53 were predisposed to diverse tumor types.
Mice with engineered "knock-outs" of the p53 gene were also tumor-prone. π§¬
This conclusion was confirmed by subsequent findings that patients with inherited mutations of p53 were predisposed to diverse tumor types.
Mice with engineered "knock-outs" of the p53 gene were also tumor-prone. π§¬
π§΅12/
Today, more than 70,000 research papers are published on p53, making it the most studied human gene in history. Mutations in p53 are found in >50% of human cancers π§¬
Today, more than 70,000 research papers are published on p53, making it the most studied human gene in history. Mutations in p53 are found in >50% of human cancers π§¬
π§΅end/
"It's impossible or very difficult to get a malignant tumor without the activity of p53 being disrupted." ~Bert Vogelstein, a legendary figure in p53 story who was the first to termed it as a tumor suppressor gene. π§¬
"It's impossible or very difficult to get a malignant tumor without the activity of p53 being disrupted." ~Bert Vogelstein, a legendary figure in p53 story who was the first to termed it as a tumor suppressor gene. π§¬
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