A naturally occurring variant of HPV-16 E7 exerts increased transforming activity through acquisition of an additional phospho-acceptor site.
Human Papillomavirus E6 and E7 play critical roles in cancer development, although not all isolates of the viral oncoproteins are identical. A common E7 variant encodes an amino acid change at N29S. We show that this change increases the levels of phosphorylation by CKII by creating an additional phospho-acceptor site at S29. This confers increased phospho-dependent interaction with a number of cellular targets, including TATA Box Binding Protein (TBP) and pRb. A further consequence is an increased ability to target pRb and p130 for degradation. Biologically, these biochemical differences are reflected in an increased ability of the N29S variant to transform primary rodent cells. This is the first study to demonstrate an important biochemical change in E7 function caused by a naturally occurring variation, and we suggest that the N29S variant merits further assessment to determine whether it has an increased association with the development of HPV-associated malignancies.
Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases/ LR11IPT04, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia; Department of Human and Experimental Pathology, Institut Pasteur de Tunis, Université Tunis el Manar, Tunis, Tunisia.
Amira
A
Zine El Abidine
Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, Italy; Division of Molecular Medicine, Rudjer Boskovic Institute, 10000 Zagreb, Croatia.
Vjekoslav
V
Tomaić
Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases/ LR11IPT04, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia.
Rahima
R
Bel Haj Rhouma
Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, Italy.
Paola
P
Massimi
Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases/ LR11IPT04, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia.
Ikram
I
Guizani
Department of Human and Experimental Pathology, Institut Pasteur de Tunis, Université Tunis el Manar, Tunis, Tunisia.
Samir
S
Boubaker
Laboratory of Molecular Epidemiology and Experimental Pathology Applied to Infectious Diseases/ LR11IPT04, Institut Pasteur de Tunis, Université Tunis El Manar, Tunis, Tunisia; Department of Human and Experimental Pathology, Institut Pasteur de Tunis, Université Tunis el Manar, Tunis, Tunisia.
Emna
E
Ennaifer
Tumour Virology Laboratory, International Centre for Genetic Engineering and Biotechnology, Padriciano 99, Trieste, Italy.
Lawrence
L
Banks
D020816:Amino Acid Motifs; D001665:Binding Sites; D002472:Cell Transformation, Viral; D052162:Human papillomavirus 16 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D050725:Papillomavirus E7 Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D030361:Papillomavirus Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D010766:Phosphorylation; D011485:Protein Binding; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000235:genetics / Q000378:metabolism
D050725:Papillomavirus E7 Proteins; D016160:Retinoblastoma Protein; D035181:TATA-Box Binding Protein; C059731:oncogene protein E7, Human papillomavirus type 16
CKII phosphorylation; E7; HPV; TBP; pRb