Identification of a peptide that disrupts hADA3-E6 interaction with implications in HPV induced cancer therapy.
Life Sci
; 288: 120157, 2022 Jan 01.
Article
en En
| MEDLINE
| ID: mdl-34801511
ABSTRACT
AIM:
High risk Human Papillomavirus (HPV) is an infectious pathogen implicated in a variety of cancers with poor clinical outcome. The mechanism of HPV induced cellular transformation and its intervention remains to be elucidated. Human ADA3 (hADA3), a cellular target of HPV16 E6, is an essential and conserved component of the ADA transcriptional coactivator complex. High risk HPV-E6 binds and functionally inactivates hADA3 to initiate oncogenesis. The aim of this study was to identify the interaction interface between hADA3 and HPV16E6 for designing inhibitory peptides that can potentially disrupt the hADA3-E6 interaction. MATERIALMETHODS:
The present investigation employed structure-based in silico tools supported by biochemical validation, in vivo interaction studies and analysis of posttranslational modifications. KEYFINDINGS:
First 3D-model of hADA3 was proposed and domains involved in the oncogenic interaction between hADA3 and HPV16E6 were delineated. Rationally designed peptide disrupted hADA3-E6 interaction and impeded malignant properties of cervical cancer cells.SIGNIFICANCE:
Intervention of hADA3-E6 interaction thus promises to be a potential strategy to combat HPV induced oncogenic conditions like cervical cancer. The investigation provides mechanistic insights into HPV pathogenesis and shows promise in developing novel therapeutics to treat HPV induced cancers.Palabras clave
Texto completo:
1
Colección:
01-internacional
Asunto principal:
Fragmentos de Péptidos
/
Proteínas Represoras
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Factores de Transcripción
/
Neoplasias del Cuello Uterino
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Proteínas Oncogénicas Virales
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Infecciones por Papillomavirus
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Dominios y Motivos de Interacción de Proteínas
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Sumoilación
Tipo de estudio:
Diagnostic_studies
/
Prognostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Life Sci
Año:
2022
Tipo del documento:
Article
País de afiliación:
India