Box 2 | Caspase activation in human papillomavirus pathogenesis

From the following article:

Human papillomavirus oncoproteins: pathways to transformation

Cary A. Moody & Laimonis A. Laimins

Nature Reviews Cancer 10, 550-560 (August 2010)

doi:10.1038/nrc2886

Although E6 and E7 act cooperatively to block apoptosis in undifferentiated cells, they induce low levels of caspase activation in differentiating cells, which are important for productive viral replication111. One of the targets of differentiation-dependent caspase activation is the E1 replication protein that acts as an origin recognition factor and helicase. E1 proteins are cleaved by caspases 3 and 7 following differentiation to presumably generate a more active replication factor. The lack of apoptosis in these differentiating cells is the result of low levels of caspase activation, coupled with an increase in anti-apoptotic proteins, such as BCL2 (Ref. 111). Human papillomavirus (HPV) infections induce ataxia telangiectasia-mutated (ATM) and CHK2 activation in differentiating keratinocytes. Caspase activation is abrogated in the presence of a CHK2 inhibitor, indicating these two pathways are linked and important for HPV genome amplification105. It is intriguing that E6 and E7 can block apoptosis in undifferentiated cells but activate low levels of caspase cleavage in differentiated cells.