**6. Regulation of E2F activity by viral oncoproteins**

Viruses work by hijacking the cellular machinery of their host cell, to facilitate their replication. Hence, it is not surprising that constitutive activation of E2F, which induces cell transition into a state of DNA replication (S-phase), is a critical step in the viral modification of infected cell functions.

#### **6.1 Human papillomavirus protein E7**

The human papillomaviruses (HPV) are commonly known oncoviruses. This notoriety is due to their ability to activate E2F proteins, causing rapid and unregulated progression through the cell cycle (Lee et al., 1998). HPV couples this action with deactivation of pathways that act as fail-safe mechanisms for E2F activity, such as p53-mediated apoptosis (Moody and Laimins, 2010). The key HPV viral protein involved in activating E2Fs is E7. This protein carries an LXCXE domain characteristic of proteins that associate with pRb family proteins (Lee et al., 1998). In this manner, E7 proteins bind to pRb, p107 and p130, dissociating them from E2F factors. The mechanisms involved in this effect include blockade by E7 of the pRb-E2F binding domain (Lee et al., 1998). As a result, E2F species bind to and activate target genes without the possibility of repression. E7 also induces pRb proteasomal degradation, by increasing its ubiquitination (Moody and Laimins). Furthermore, there is evidence to indicate that E7 also binds to p300/CBP, allowing this acetyltransferase to facilitate and rapidly increase the transcription of E2F target genes (Bernat et al., 2003).
