Human papillomaviruses and the specificity of PDZ domain targeting.
The human papillomavirus (HPV) E6 oncoprotein is fundamental to the ability of these viruses to induce human malignancy. A defining characteristic of the HPV E6 oncoproteins found in cancer-causing HPV types is the presence of a PDZ binding motif at their extreme C-terminus. Through this motif, E6 is able to interact with a large number of cellular proteins that contain PDZ domains. Many of these cellular proteins are involved in regulation of processes associated with the control of cell attachment, cell proliferation, cell polarity and cell signaling. How E6 targets multiple proteins containing the same recognition domain is still an open question. In this review, we highlight aspects of E6 function and biology that help to answer this question, and thereby provide insight into the role of these substrates during development of HPV-induced malignancy.
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
David
D
Pim
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Martina
M
Bergant
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Siaw S
SS
Boon
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Ketaki
K
Ganti
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Christian
C
Kranjec
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Paola
P
Massimi
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Vanitha K
VK
Subbaiah
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Miranda
M
Thomas
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Vjekoslav
V
Tomaić
International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
Lawrence
L
Banks
D006801:Humans; D009369:Neoplasms / Q000378:metabolism / Q000821:virology*; D009856:Oncogene Proteins, Viral / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054731:PDZ Domains / Q000502:physiology*; D027383:Papillomaviridae / Q000302:isolation & purification; D030361:Papillomavirus Infections / Q000378:metabolism* / Q000821:virology; D013379:Substrate Specificity
D009856:Oncogene Proteins, Viral