Question

Human papillomavirus (HPV) is a causative factor in over \(95 \%\) of cervical cancers. Other viruses such as Epstein-Barr, Kaposi's sarcoma-associated herpes virus, and hepatitis B virus also are known to cause cancer. For this to happen, viral genes that promote entry into Sphase or that promote resistance to apoptosis must become incorporated into the host cell DNA in a host cell that also survives the viral infection. If the viral gene within the host DNA is then overexpressed in an unregulated manner, it is a viral oncogene. A viral protein could bind to cellular \(\mathrm{P} 53\) and promote its degradation. P53, which is an inducer of apoptosis, A. is activated by kinases located in chromatin. B. increases the transcription of several pro-apoptotic genes for Bd- 2 protcins. C. concentration is normally low because it is subject to ubiquitination. D. concentration may be increased by acetylation. E. all of the above.

Short answer

A. P53 is a transcription factor that is activated in response to DNA damage signals and is regulated by kinases such as ATM, ATR, and DNA-PK. B. P53 increases the transcription of pro-apoptotic genes from the Bd-2 protein family. C. P53 is regulated by ubiquitination which targets it for degradation by the proteasome. D. Acetylation can increase the stability and activity of P53. Answer: E. A, C, and D are correct.

Step-by-step solution

Examine each statement

We will analyze each statement to determine if it is true or false regarding P53 and its function. A. P53 is a transcription factor that is activated in response to DNA damage signals. Its activation is indeed regulated by kinases such as ATM, ATR, and DNA-PK, which are located in the chromatin. Hence, statement A is true. B. P53 is known to increase the transcription of several pro-apoptotic genes. These genes include Bax, Bad, and Noxa, which belong to the Bcl-2 protein family, but not the Bd-2 protein family as stated in the exercise. Therefore, statement B is false. C. Under normal circumstances, P53 is regulated by ubiquitination which targets it for degradation by the proteasome. This is a way of keeping P53 concentration low in the cell when it is not needed. Thus, statement C is true. D. Acetylation is a post-translational modification that can increase the stability and activity of P53. Acetylation can prevent P53 from being ubiquitinated, leading to an increase in its concentration. Therefore, statement D is true.

Choose the correct answer

We have analyzed each statement and identified whether it is true or false. According to our analysis, statements A, C, and D are true, while statement B is false. Thus, the correct answer is: E. all of the above.

Key concepts

Viral Oncogenes

Viral oncogenes are a critical topic in the study of cancer biology and virology. Put simply, they are genes that originate from viruses, which, when incorporated into the DNA of a host cell, can contribute to the development of cancer.

How does this happen? When a virus infects a cell, it sometimes inserts its own genetic material into the host's DNA. This is a regular part of the life cycle for many viruses. However, when the inserted genetic material includes genes that encourage the host cell to continuously divide (pushing the cell into the S phase of the cell cycle) or genes that confer resistance to programmed cell death (apoptosis), the infected cell can start behaving like a cancer cell.

Not all viral genes are oncogenic, but the ones that are can cause normal cells to become cancerous by disrupting normal regulatory mechanisms. For example, a viral oncogene might overstimulate cell division or inhibit the natural cell death processes that eliminate potentially dangerous cells. This overexpression of viral oncogenes is dangerous and can lead to the formation of tumors.

Human Papillomavirus (HPV)

Human papillomavirus (HPV) poses a significant risk factor for developing cervical cancer as well as other types of cancers. It is a common virus with many different types, some of which are referred to as 'high-risk' due to their association with cancer.

HPV infects epithelial cells—the cells that line body surfaces—and can lead to cellular changes. This is precisely because HPV can insert its DNA into that of the host's cells. Certain types of HPV contain oncogenes that can disrupt cell cycle regulation. These oncogenes can bind to and degrade tumor suppressor proteins, such as p53 and Rb (retinoblastoma protein), which are vital to regulating cell growth and apoptosis.

By neutralizing these tumor suppressors, the high-risk HPV types can lead to uncontrolled cell division and the eventual development of cancerous growths. The link between HPV and cervical cancer illustrates how viruses can play a direct role in the genesis of cancer.

DNA Damage Response

The DNA damage response is an essential cellular defense mechanism against various types of damage to DNA. This is a complex system involving detection of the damage, signal transduction, and eventual repair of the damage or activation of apoptosis if the damage is irreparable.

Proteins like p53 play prominent roles in the DNA damage response. When DNA damage occurs, p53 is activated through phosphorylation by kinases, a detail that directly ties into the step-by-step solution discussed previously. P53 then functions as a transcription factor that can either halt cell division, allowing time for DNA repair, or activate the expression of genes involved in apoptosis.

The accuracy of the DNA damage response is critical for preventing mutations and maintaining genomic integrity. If this response is circumvented—as it can be by some viral oncogenes, such as those from HPV—the result may be the survival and proliferation of damaged cells, contributing to cancer development.

P53's role in apoptosis and DNA repair underscores its importance as a tumor suppressor, and its inactivation by viral proteins or other mutations is a hallmark in many types of cancer.