Growth suppression induced by downregulation of E6-AP expression in human papillomavirus-positive cancer cell lines depends on p53.
The ubiquitin-protein ligase E6-AP is utilized by the E6 oncoprotein of human papillomaviruses (HPVs) associated with cervical cancer to target the tumor suppressor p53 for degradation. Here, we report that downregulation of E6-AP expression by RNA interference results in both the accumulation of p53 and growth suppression of the HPV-positive cervical cancer cell lines HeLa and SiHa. In addition, HeLa cells, in which p53 expression was suppressed by RNA interference, are significantly less sensitive to the downregulation of E6-AP expression with respect to growth suppression than parental HeLa cells. These data indicate that the anti-growth-suppressive properties of E6-AP in HPV-positive cells depend on its ability to induce p53 degradation.
Hengstermann
Arnd
A
Center for Biochemistry, Faculty of Medicine, University of Cologne, Germany.
D'silva
Michael A
MA
Kuballa
Petric
P
Butz
Karin
K
Hoppe-Seyler
Felix
F
Scheffner
Martin
M
D015536:Down-Regulation; D005260:Female; D006367:HeLa Cells; D006801:Humans; D027383:Papillomaviridae / Q000302:isolation & purification*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000627:therapeutic use; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*; D044767:Ubiquitin-Protein Ligases / Q000037:antagonists & inhibitors* / Q000235:genetics; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000628:therapy* / Q000821:virology*
D034741:RNA, Small Interfering; D016159:Tumor Suppressor Protein p53; C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases