HDAC inhibitors trigger apoptosis in HPV-positive cells by inducing the E2F-p73 pathway

Patrick Finzer*, Andreas Krueger, Michael Stöhr, Dirk Brenner, Ubaldo Soto, Christian Kuntzen, Peter H. Krammer, Frank Rösl

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

41 Citations (Scopus)


Histone deacetylase (HDAC) inhibitors induce an intrinsic type of apoptosis in human papillomavirus (HPV)-positive cells by disrupting the mitochondrial transmembrane potential (ΔΨm). Loss of ΔΨ m was only detected in E7, but not in E6 oncogene-expressing cells. HDAC inhibition led to a time-dependent degradation of the pocket proteins pRb, p107 and p130, releasing 'free' E2F-1 following initial G1 arrest. Inhibition of proteasomal proteolysis, but not of caspase activity rescued pRb from degradation and functionally restored its inhibitory effect on the cyclin E gene, known to be suppressed by pRb-E2F-1 in conjunction with HDAC1. Using siRNA targeted against p53, E2F-1 still triggered apoptosis by inducing the E2F-responsive proapoptotic α- β-isoforms of p73. These data may determine future therapeutic strategies in which HDAC inhibitors can effectively eliminate HPV-positive cells by an apoptotic route that does not rely on the reactivation of the 'classical' p53 pathway through a preceding shut-off of viral gene expression.

Original languageEnglish
Pages (from-to)4807-4817
Number of pages11
Issue number28
Publication statusPublished - 17 Jun 2004
Externally publishedYes


  • Cervical carcinoma cells
  • HDAC inhibitors
  • Human papillomavirus


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