Escape of p53 protein from E6-mediated degradation in HeLa cells after cisplatin therapy

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WESIERSKA-GADEK Jozefa SCHLOFFER Daniela KOTALA Vladimír HORKÝ Marcel

Rok publikování 2002
Druh Článek v odborném periodiku
Časopis / Zdroj International Journal of Cancer
Fakulta / Pracoviště MU

Lékařská fakulta

Citace
Obor Genetika a molekulární biologie
Klíčová slova apoptosis; nucleolar segregation; E6; cisplatin; PARP-1
Popis We previously reported that therapy of human cervical carcinoma HeLa cells with CP induced segregation of nucleoli and changes of nuclei characteristic of apoptosis. We raised the question of whether p53 can be reactivated by chemotherapy in HeLa cells despite the presence of HPV-encoded E6 activity. Since the reduced stability of wild-type p53 protein in HeLa cells is a consequence of its enhanced ubiquitination by virally encoded E6 protein, resulting in its accelerated degradation, we checked the cellular level of E6 during CP therapy. Six hours after application of CP, E6 protein expression was markedly reduced. This coincided with the increase of cellular p53 and preceded the nucleolar accumulation of p53 protein, indicating that repression of virally coded E6 protein by CP contributes to the restoration of p53 expression.
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