Degradation of p53 by natural variants of the E6 protein of human papillomavirus type 16

Abstract

The degradation of p53 by high-risk human papillomavirus (HR-HPV) E6 proteins is recognized as necessary for the immortalization of mammary epithelial cells and the progression of cancer. The HR-HPV type 16 E6 proteins exhibit numerous variants associated with different risk factors for the development of cervical cancer. Two variants of E6 proteins, D25E and L83V, are common in cervical carcinomas among Asian and European populations. In the present study, we compared the effect of two E6 variants on p53 degradation by a prototype E6 protein. We demonstrate that both the D25E and L83V variants downregulate p53 through a ubiquitin-proteasome pathway, and that the effect is very similar to that of the prototype E6 protein. The reduction in the p53 protein levels was induced through the ubiquitin-proteasome pathway via interaction with E6 proteins. The expression of p21 CIP1/WAF1, a downstream molecule of p53, was similarly reduced in both prototype and variant E6 protein-expressing cell lines, leading to aberrant G1/S cell cycle arrest. These results suggest that the natural variants, E6 D25E and L83V, similar to the prototype E6 protein, contribute to tumorigenesis by degrading p53.

Ocular squamous cell carcinoma in Holstein cows from the South of Brazil

“…Some viral infections also can also play a role in carcinogenesis due to viral binding on p53 gene [ 40 , 43 ]. Even though there are Brazilian regions with much higher UVI, the animals investigated here lived in a still considerably sunny subtropical location where the UVI varies from medium (3.5 UVI) during the winter to the extreme (13.4 UVI) during the summer months [ 46 ]. Thus, it is conceivable that mutations induced by ultraviolet rays had some influence in the etiology of OSCC.…”

Mucosal human papillomavirus detection and TP53 immunohistochemical expression in non‐melanoma skin cancer in Tunisian patients

“…Cutaneous HPVs are the most commonly identified HPV types in skin cancer; but mucosal HPV (mHPV) types have been also widely investigated in skin carcinogenesis, in view of their frequent involvement in cervical cancer . mHPVs act as an oncogenic factor by degradation of two principal proteins: tumor protein 53 (TP53) (involved in the regulation of cell cycle, apoptosis, and maintenance of genomic stability) and the retinoblastoma protein (pRB) (involved in the inhibition of the G1 to S phase transition in the cell cycle) . This role was clearly identified in cervical, anogenital, and some oropharyngeal carcinomas.…”

Phosphorus-32, a Clinically Available Drug, Inhibits Cancer Growth by Inducing DNA Double-Strand Breakage

“…Antibody directed against beta-actin was used to verify equal loading of protein amounts in the gel wells. HeLa S3 cells express E6 from HPV18 and are rendered p53 null which severely inhibits apoptosis functions [ 28 , 29 ].…”