The human papillomavirus E7 proteins associate with p190RhoGAP and alter its function.

Area of Science:

• Molecular biology
• Virology
• Cell biology

Background:

• The human papillomavirus (HPV) E7 protein is a key oncogene involved in viral-induced cancers.
• p190RhoGAP (p190) is a GTPase-activating protein (GAP) that regulates RhoA, influencing cell migration and cytoskeletal organization.

Purpose of the Study:

• To identify cellular binding partners of the HPV16 E7 protein.
• To investigate the functional consequences of the interaction between HPV E7 and p190RhoGAP.

Main Methods:

• Mass spectrometry was used to identify p190 as an HPV16 E7 binding partner.
• Interaction studies were performed using various HPV E7 proteins and p190 mutants.
• Mutagenesis of conserved region 3 (CR3) in E7 identified key residues for p190 binding.

Main Results:

• p190RhoGAP (p190) was identified as a novel binding partner for HPV E7.
• E7 proteins from multiple HPV types bind to p190, with CR3 of E7 and the middle domain of p190 being crucial for interaction.
• The E7-p190 interaction dysregulates p190, alters the actin cytoskeleton, and negatively impacts cell spreading on fibronectin.

Conclusions:

• The interaction between HPV E7 and p190RhoGAP is conserved across HPV types and has significant biological consequences.
• This interaction likely contributes to the HPV life cycle and the development of HPV-induced tumors by altering cellular processes like actin organization and cell migration.