Growth inhibition of HeLa cells is a conserved feature of high-risk human papillomavirus E8
J Virol
; 85(6): 2918-26, 2011 Mar.
Article
em En
| MEDLINE
| ID: mdl-21191025
ABSTRACT
Infections with certain human papillomaviruses (HPV), such as type 16 (HPV16), 18, or 31, are a necessary risk factor for the development of cervical cancer. Transcript analyses of several HPV revealed that the viral E2 gene encodes both the E2 regulator protein and the E8â§E2C protein, which differ in their amino termini. Up to now, functional studies have focused on HPV31 E8â§E2C and demonstrated that it is a potent repressor of viral transcription and replication. However, recent analyses of HPV16 genomes have suggested that E8â§E2C proteins may differ in their activities. Therefore, we performed a comparative analysis of E8â§E2C proteins of HPV16, -18, and -31. All E8â§E2C proteins potently inhibited HPV E6/E7 oncogene promoters, and also displayed long-distance transcriptional-repression activities. Furthermore, the expression of all E8â§E2C proteins inhibited the growth of HeLa cells. Expression of E8â§E2C proteins rapidly increased the protein levels of the E6 and E7 targets p53 and p21, consistent with the repression of the endogenous HPV18 E6/E7 promoter. All E8â§E2C proteins induced G(1) arrest more efficiently than E2 proteins and activated senescence markers. Furthermore, we demonstrate that the 31E8 domain can be functionally replaced by the KRAB repression domain derived from KOX1. The KRAB-E2C fusion protein possesses long-distance transcriptional-repression activity and inhibits the growth of HeLa cells comparably to E8â§E2C. Taken together, our results suggest that the E8â§E2C proteins of HPV16, -18, and -31 are highly conserved transcriptional repressors that inhibit the growth of HeLa cells by repression of E6/E7 transcription but do not have proapoptotic activities.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Repressoras
/
Regulação Viral da Expressão Gênica
/
Proteínas Oncogênicas Virais
/
Células Epiteliais
/
Papillomavirus Humano 16
/
Papillomavirus Humano 18
/
Papillomavirus Humano 31
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2011
Tipo de documento:
Article