Apoptosis inhibition by the human DEK oncoprotein involves interference with p53 functions.

Area of Science:

• Oncology
• Molecular Biology
• Cell Biology

Background:

• The DEK proto-oncogene is linked to human carcinogenesis through fusion or upregulation.
• Intracellular functions of DEK remain largely uncharacterized.
• DEK expression is induced by high-risk human papillomavirus (HPV) E7 protein, inhibiting cellular senescence.

Purpose of the Study:

• To investigate the role of DEK in cellular proliferation and survival.
• To determine if DEK expression is necessary for cell survival.
• To elucidate the mechanism by which DEK influences cell death.

Main Methods:

• Knockdown of DEK expression in cancer and primary human cells.
• Monitoring cellular responses, including apoptosis.
• Assessing the stability and transcriptional activity of the p53 tumor suppressor.
• Utilizing a p53-negative cell line (SAOS-2) and dominant-negative p53 miniprotein.

Main Results:

• DEK expression protects both HPV-positive cancer and primary human cells from apoptotic cell death.
• DEK depletion leads to increased p53 protein stability and transcriptional activity, upregulating p53 target genes (p21CIP, Bax).
• p53-negative cells (SAOS-2) were resistant to DEK knockdown, and dominant-negative p53 inhibited DEK RNA interference-induced cell death.

Conclusions:

• DEK plays a novel role in cellular survival by destabilizing p53.
• DEK-mediated p53 destabilization likely contributes to human carcinogenesis.
• DEK's interaction with p53 and its role in apoptosis inhibition offer new insights into cancer mechanisms.