Human papilloma virus E7 oncoprotein abrogates the p53-p21-DREAM pathway

Area of Science:

• Oncology
• Molecular Biology
• Virology

Background:

• High-risk human papillomaviruses (HPVs) are oncogenic, with E6 and E7 oncoproteins driving cancer development.
• HPV E7 targets the retinoblastoma protein (pRB) and, more recently, the DREAM transcriptional repressor complex.
• The p53-p21-DREAM pathway is crucial for cell cycle checkpoint activation, with p53 downregulating DREAM targets.

Purpose of the Study:

• To identify genes deregulated by HPV E7 expression genome-wide.
• To investigate the relationship between E7-deregulated genes, cell cycle genes, and DREAM targets.
• To determine if HPV E7 impairs p53-mediated cell cycle control.

Main Methods:

• Genome-wide gene expression analysis of HPV E7-expressing cells.
• Comparison with datasets of cell cycle-regulated genes and known DREAM targets.
• Analysis of p53-dependent gene regulation in the presence and absence of HPV E7.

Main Results:

• HPV E7 expression leads to widespread deregulation of DREAM target genes.
• E7 expression abrogates p53-dependent downregulation of DREAM targets.
• Most cell cycle genes are upregulated upon E7 expression, indicating cell cycle dysregulation.

Conclusions:

• HPV E7 oncoprotein disrupts the DREAM complex, leading to cell cycle gene upregulation.
• E7 impairs p53's ability to control cell cycle checkpoints, independent of the E6 oncoprotein.
• This disruption of cell cycle control by HPV E7 contributes to oncogenesis.