The Human Papillomavirus (HPV) E6 Oncoprotein Regulates CD40 Expression via the AT-Hook Transcription Factor AKNA

Cancers

Joaquin Manzo-Merino¹  CarlaO. Contreras-Ochoa²  Alicia Román-Gonzalez²  Alfredo Lagunas-Martínez²  Crysele Calderón-Corona²  Kirvis Torres-Poveda²  Margarita Bahena-Román²  Vicente Madrid-Marina²  Rogelio Hernández-Pando³  Marcela Lizano⁴  LeonardoJ. Castro-Muñoz⁴ 

[1] CONACyT-Instituto Nacional de Cancerología, Mexico City 14080, Mexico;Chronic Infections and Cancer Division, Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Instituto Nacional de Salud Pública, Secretaría de Salud, Avenida Universidad 655, Col. Santa María Ahuacatitlan, Cuernavaca, Morelos 62100, Mexico;Section of Experimental Pathology, Department of Pathology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City 14080, Mexico;Unidad de Investigación Biomédica en Cáncer, Instituto Nacional de Cancerología-Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, Mexico City 14080, Mexico;

关键词: HR-HPV;    AKNA;    E6 oncoprotein;    CD40;    p53;    proteasome;   

DOI  :  10.3390/cancers10120521

来源: DOAJ

【 摘 要 】

Persistent infection with high-risk Human Papillomavirus (HR-HPV) is the main requisite for cervical cancer development. Normally, HPV is limited to the site of infection and regulates a plethora of cellular elements to avoid the immune surveillance by inducing an anti-inflammatory state, allowing the progress through the viral cycle and the carcinogenic process. Recent findings suggest that the AT-hook transcriptional factor AKNA could play a role in the development of cervical cancer. AKNA is strongly related to the expression of co-stimulatory molecules such CD40/CD40L to achieve an anti-tumoral immune response. To date, there is no evidence demonstrating the effect of the HPV E6 oncoprotein on the AT-hook factor AKNA. In this work, minimal expression of AKNA in cervical carcinoma compared to normal tissue was found. We show the ability of E6 from high-risk HPVs 16 and 18 to interact with and down-regulate AKNA as well as its co-stimulatory molecule CD40 in a proteasome dependent manner. We also found that p53 interacts with AKNA and promotes AKNA expression. Our results indicate that the de-regulation of CD40 and AKNA is induced by the HPV E6 oncoprotein, and this event involves the action of p53 suggesting that the axis E6/p53A/AKNA might play an important role in the de-regulation of the immune system during the carcinogenic process induced by HR-HPV.

【 授权许可】

Unknown