Oncogenes of HPV

Key Concepts:

• Growth Factor Signaling
• CDK Cyclin
• Retinoblastoma Protein (pRb)
• Cell Cycle (G1 to S phase)
• Human Papillomavirus (HPV)
• E6 and E7 proteins
• Tumor Suppressor Proteins
• DNA Damage
• p53
• Apoptosis (Programmed Cell Death)
• Cell Proliferation
• Tumor Formation

1. Normal Cell Growth Regulation (No HPV Infection):

• Growth Factor Binding: When a growth factor binds to a receptor on a normal human cell (without HPV infection), it initiates a signaling cascade.
• CDK Cyclin Activation: This signaling stimulates the activity of CDK (Cyclin-Dependent Kinase) cyclin complexes.
• pRb Phosphorylation and Inactivation: The activated CDK cyclin phosphorylates the retinoblastoma protein (pRb), a tumor suppressor protein. Phosphorylation inactivates pRb.
• Cell Cycle Progression: Inactive pRb allows the cell to progress from the G1 phase to the S phase of the cell cycle, enabling cell proliferation.
  • Note: The transcript states "as a result the cell cannot proliferate" which is incorrect. Inactive pRb allows cell proliferation.

2. HPV Infection and pRb Degradation:

• E7 Protein Production: Upon HPV infection, the virus produces proteins, including E7.
• E7 Binding to pRb: The E7 protein binds to active (unphosphorylated) pRb.
• pRb Degradation: This binding triggers the degradation of pRb.
• Uncontrolled Cell Proliferation: Without functional pRb, the cell cycle is no longer properly regulated, leading to uncontrolled cell proliferation and potentially tumor formation.
  • Note: The transcript states "the cell cannot progress from g1 to s phase of the cell cycle" which is incorrect. Without pRb, the cell can progress uncontrollably.

3. Normal Response to DNA Damage (No HPV Infection):

• DNA Damage Detection: If DNA damage occurs due to factors like radiation or chemicals, it activates another tumor suppressor protein, p53.
• p53 Activation of Apoptosis: Activated p53 initiates apoptosis, or programmed cell death.
• Elimination of Damaged Cells: This process eliminates cells with damaged DNA, preventing them from proliferating and forming tumors.

4. HPV Infection and p53 Degradation:

• E6 Protein Production: HPV infection also leads to the production of the E6 protein.
• E6 Binding to p53: The E6 protein binds to the host cell's p53 protein.
• p53 Degradation: This binding causes the degradation of p53.
• Impaired Apoptosis: Consequently, if DNA damage occurs in an HPV-infected cell, there is no functional p53 available to trigger apoptosis.
• Survival and Proliferation of Damaged Cells: The cell with damaged DNA survives and begins to proliferate, increasing the risk of tumor formation.

5. Logical Connections:

• The video contrasts the normal cellular mechanisms for controlling cell growth and responding to DNA damage with the ways in which HPV disrupts these mechanisms.
• The E6 and E7 proteins of HPV are presented as key factors in promoting uncontrolled cell proliferation by targeting and degrading the tumor suppressor proteins p53 and pRb, respectively.
• The absence of functional p53 and pRb removes critical checkpoints in the cell cycle and DNA damage response, leading to increased risk of tumor development.

6. Synthesis/Conclusion:

The video explains how HPV infection promotes tumor formation by interfering with two crucial tumor suppressor pathways. The E7 protein degrades pRb, disrupting cell cycle control, while the E6 protein degrades p53, disabling the DNA damage response and apoptosis. This dual disruption allows cells with damaged DNA to proliferate unchecked, ultimately leading to tumor development. The key takeaway is that HPV's ability to disable these tumor suppressor proteins is central to its oncogenic potential.