Which viral protein is responsible for inactivation of the p53 tumor suppressor in HPV-mediated cervical carcinogenesis?

Explanation

## HPV Oncoproteins and Tumor Suppressor Inactivation **Key Point:** The HPV E6 protein specifically targets and degrades p53, the "guardian of the genome," through proteasomal degradation via ubiquitin-dependent pathways. ### HPV Proteins: Structure and Function | Protein | Type | Function | Role in Carcinogenesis | |---------|------|----------|------------------------| | E6 | Early protein | Ubiquitin ligase adaptor | Inactivates p53 (degradation) | | E7 | Early protein | Viral oncoprotein | Inactivates Rb (sequestration) | | L1 | Late protein | Major capsid protein | Structural; no oncogenic role | | L2 | Late protein | Minor capsid protein | Structural; no oncogenic role | ### Mechanism of p53 Inactivation by E6 1. E6 protein binds to E6-associated protein (E6AP), an E3 ubiquitin ligase 2. E6–E6AP complex recruits p53 to the proteasome 3. p53 is polyubiquitinated and degraded 4. Loss of p53 → loss of cell cycle checkpoints, apoptosis evasion, and genomic instability **High-Yield:** E6 and E7 are the two critical viral oncoproteins; **E6 = p53 killer**, **E7 = Rb killer**. Together they disable both major tumor suppressor pathways. **Clinical Pearl:** p53 mutations are found in ~50% of sporadic cancers but are rare in HPV-positive cervical cancers because E6 functionally inactivates p53 without genetic mutation. **Mnemonic:** **E6 → p53** (both have "5" in them — E**6** inactivates p**53**). **E7 → Rb** (E**7** inactivates **Rb** — both have round-sounding names).