Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses - PubMed (original) (raw)

Review

Cellular transformation by human papillomaviruses: lessons learned by comparing high- and low-risk viruses

Aloysius J Klingelhutz et al. Virology. 2012.

Abstract

The oncogenic potential of papillomaviruses (PVs) has been appreciated since the 1930s yet the mechanisms of virally-mediated cellular transformation are still being revealed. Reasons for this include: a) the oncoproteins are multifunctional, b) there is an ever-growing list of cellular interacting proteins, c) more than one cellular protein may bind to a given region of the oncoprotein, and d) there is only limited information on the proteins encoded by the corresponding non-oncogenic PVs. The perspective of this review will be to contrast the activities of the viral E6 and E7 proteins encoded by the oncogenic human PVs (termed high-risk HPVs) to those encoded by their non-oncogenic counterparts (termed low-risk HPVs) in an attempt to sort out viral life cycle-related functions from oncogenic functions. The review will emphasize lessons learned from the cell culture studies of the HPVs causing mucosal/genital tract cancers.

Copyright © 2011 Elsevier Inc. All rights reserved.

PubMed Disclaimer

Figures

Fig. 1

Fig. 1

Schematic of the HPV 16 E6 protein. The two zinc binding sites are conserved among the different HPV types. Protein binding regions are shown for HPV 16 E6. The text below the schematic displays the aligned sequences of high-risk HPV 6 E6 and low-risk HPV 16 E6.

Fig. 2

Fig. 2

Schematic of the HPV 16 E7 protein. The positions of CR1, CR2, and the zinc binding site, as well as the LXCXE motif and CKII site within CR2 are shown. The zinc binding site is conserved among the different HPV types. Protein binding regions are shown for HPV 16 E7. The text below the schematic displays the aligned sequences of high-risk HPV 6 E7 and HPV 16 E7. The PTLHE (6–10), DLYC (22–26) sequences referred to in the text are underlined; the amino acid conferring low or high Rb binding affinity is italicized; the PKC site in HPV 6 E7 is in purple; the LXCXE motif in red; and the CKII recognition sequence in blue. The proximity of the sequences required for abrogating p21CIP1 activity (aa 68–70 and 79–83) and for binding HDAC is denoted by underlining and brown lettering, respectively.

Similar articles

Cited by

References

    1. Accardi R, Dong W, Smet A, Cui R, Hautefeuille A, Gabet AS, Sylla BS, Gissmann L, Hainaut P, Tommasino M. Skin human papillomavirus type 38 alters p53 functions by accumulation of deltaNp73. EMBO Rep. 2006;7:334–340. - PMC - PubMed
    1. Ai W, Toussaint E, Roman A. CCAAT displacement protein binds to and negatively regulates human papillomavirus type 6 E6, E7, and E1 promoters. J Virol. 1999;73:4220–4229. - PMC - PubMed
    1. Ai W, Narahari J, Roman A. Yin yang 1 negatively regulates the differentiation-specific E1 promoter of human papillomavirus type 6. J Virol. 2000;74:5198–5205. - PMC - PubMed
    1. Akgul B, Garcia-Escudero R, Ghali L, Pfister HJ, Fuchs PG, Navsaria H, Storey A. The E7 protein of cutaneous human papillomavirus type 8 causes invasion of human keratinocytes into the dermis in organotypic cultures of skin. Cancer Res. 2005;65:2216–2223. - PubMed
    1. Alfandari J, Shnitman Magal S, Jackman A, Schlegel R, Gonen P, Sherman L. HPV16 E6 oncoprotein inhibits apoptosis induced during serum-calcium differentiation of foreskin human keratinocytes. Virology. 1999;257:383–396. - PubMed

Publication types

MeSH terms

Substances

LinkOut - more resources