Degradation of p53 by HPV16-E6 variants isolated from cervical cancer specimens of Moroccan women

•HPV16-E6 European (E), African (Af) and North American (NA) variants degrade p53 variously, with improved oncogenic potential for Af variants.•Af variants (Af2-a/r, Af1-d/G295 and Af2-/aG285) harbor Q14D, R10G and R10I mutations, which occur in Gln14 and Arg10 sites that are involved in the binding...

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Veröffentlicht in:Gene 2021-07, Vol.791, p.145709-145709, Article 145709
Hauptverfasser: HADAMI, Khaoula, SABY, Charles, DAKKA, Nadia, COLLIN, Guillaume, ATTALEB, Mohammed, KHYATTI, Meriem, FILALI-MALTOUF, Abdelkarim, MORJANI, Hamid, EL MZIBRI, Mohammed
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Sprache:eng
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Zusammenfassung:•HPV16-E6 European (E), African (Af) and North American (NA) variants degrade p53 variously, with improved oncogenic potential for Af variants.•Af variants (Af2-a/r, Af1-d/G295 and Af2-/aG285) harbor Q14D, R10G and R10I mutations, which occur in Gln14 and Arg10 sites that are involved in the binding interface of E6-p53 core domain.•Q14D, R10G and R10I mutations could affect the E6-p53 interaction, and so, the degradation of p53.•The effect of E6 mutations can extend to impaired anti-E6 therapeutic efficacy. Cervical cancer is the second most diagnosed cancer in Moroccan women. The main etiological factor for developing cervical cancer is the persistent infection with HPV16. Genetic studies have reported the occurrence of amino acid variations within the E6 oncoprotein that promotes host cell transformation by targeting p53 for degradation. To verify the biological effects of E6 polymorphisms towards p53 degradation, HPV16-E6 prototype and 7 variants isolated from cervical cancer biopsies of Moroccan women were evaluated for their activities by transient expression assays using pcDNA3.1-E6 constructs in C33A cell line. Expression of E6 genes in transfected cells was detected with reverse transcription PCR (RT-PCR), then, p53 levels were evaluated by western blot analysis. Significant dissimilarities in p53 degradation activities of HPV16-E6 prototype and intratypic variants were noticed. As compared to the prototype, the highest p53 degradation were exhibited by the African variants Af2-a/r, Af1-d/G295 and Af2-a/G285 (p 
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2021.145709