Binding of human papillomavirus 16 E6 to p53 and E6AP is impaired by monoclonal antibodies directed against the second zinc-binding domain of E6

The E6 protein of cancer-associated human papillomavirus type 16 (16E6) binds to p53 and, in association with E6AP, promotes its degradation through the ubiquitin–proteasome pathway. The aim of this work was to develop monoclonal antibodies against 16E6 and to test their effect on the binding of 16E6 to p53 and E6AP, and on the degradation of p53. It was shown that an antibody directed against the N terminus of 16E6 inhibited E6AP-dependent binding to p53 and degradation of p53, whereas two different antibodies directed to the second zinc-binding domain of 16E6 reduced 16E6 E6AP-independent binding to p53 and binding to E6AP but not degradation of p53.

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The carboxyl-terminal zinc-binding domain of the human papillomavirus E7 protein can be functionally replaced by the homologous sequences of the E6 protein

Virus Research ◽

10.1016/s0168-1702(97)00090-7 ◽

1997 ◽

Vol 52 (1) ◽

pp. 109-118 ◽

Cited By ~ 12

Author(s):

Kreton O Mavromatis ◽

D.Leanne Jones ◽

Rupa Mukherjee ◽

Carole Yee ◽

Miranda Grace ◽

...

Keyword(s):

Human Papillomavirus ◽

Binding Domain ◽

Zinc Binding ◽

Homologous Sequences ◽

Carboxyl Terminal ◽

Zinc Binding Domain ◽

E6 Protein

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Patterns of CD8 T-Cell Epitopes within the Human Papillomavirus Type 16 (HPV 16) E6 Protein among Young Women Whose HPV 16 Infection Has Become Undetectable

Clinical and Diagnostic Laboratory Immunology ◽

10.1128/cdli.12.8.1003-1005.2005 ◽

2005 ◽

Vol 12 (8) ◽

pp. 1003-1005 ◽

Cited By ~ 11

Author(s):

Mayumi Nakagawa ◽

Kevin H. Kim ◽

Anna-Barbara Moscicki

Keyword(s):

Human Papillomavirus ◽

T Cell ◽

Cd8 T Cell ◽

Recombinant Vaccinia Virus ◽

T Cell Epitopes ◽

Hpv 16 ◽

Human Papillomavirus 16 ◽

Human Papillomavirus Type 16 ◽

T Cell Lines ◽

E6 Protein

ABSTRACT The patterns of CD8 T-cell epitopes recognized within the E6 protein in women who had cleared their human papillomavirus 16 infection were examined. T-cell lines were established using autologous dendritic cells infected with a recombinant vaccinia virus. Evidence of potential antigenic epitopes was shown in 8 of 23 (34.8%) women.

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Single-domain antibodies represent novel alternatives to monoclonal antibodies as targeting agents against the human papillomavirus 16 E6 protein

10.1101/388884 ◽

2018 ◽

Cited By ~ 1

Author(s):

Melissa Togtema ◽

Greg Hussack ◽

Guillem Dayer ◽

Megan Teghtmeyer ◽

Shalini Raphael ◽

...

Keyword(s):

Monoclonal Antibodies ◽

Human Papillomavirus ◽

Human Papillomavirus 16 ◽

E6 Oncoprotein ◽

Phage Display Libraries ◽

Variable Domains ◽

Therapeutic Molecules ◽

E6 Protein

AbstractApproximately one-fifth of all malignancies worldwide are etiologically-associated with a persistent viral or bacterial infection. Thus, there is particular interest in therapeutic molecules which utilize components of a natural immune response to specifically inhibit oncogenic microbial proteins, as it is anticipated they will elicit fewer off-target effects than conventional treatments. This concept has been explored in the context of human papillomavirus type 16 (HPV16)-related cancers, through the development of monoclonal antibodies and fragments thereof against the viral E6 oncoprotein. However, challenges related to the biology of E6 as well as the functional properties of the antibodies themselves appear to have precluded their clinical translation. In this study, we attempted to address these issues by exploring the utility of the variable domains of camelid heavy-chain-only antibodies (denoted as VHHs). Through the construction and panning of two llama immune VHH phage display libraries, a pool of potential VHHs was isolated. The interactions of these VHHs with recombinant E6 protein were further characterized using ELISA, Western blotting under both denaturing and native conditions, as well as surface plasmon resonance, and three antibodies were identified that bound recombinant E6 with affinities in the nanomolar range. Our results now lead the way for subsequent studies into the ability of these novel molecules to inhibit HPV16-infected cellsin vitroandin vivo.

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