E2F-1 potentiates cell death by blocking antiapoptotic signaling pathways

Mol Cell. 1999 Nov;4(5):771-81. doi: 10.1016/s1097-2765(00)80387-1.

Abstract

The E2F family of transcription factors plays an essential role in promoting cell cycle progression, and one member of the family, E2F-1, is also capable of inducing apoptosis. We show here that E2F-1 can induce apoptosis by a death receptor-dependent mechanism, by downregulating TRAF2 protein levels and inhibiting activation of antiapoptotic signals including NF-kappa B. In this way, E2F-1 expression can lead to the sensitization of cells to apoptosis by a number of agents independently of p53. Deregulation of E2F-1 activity occurs in the majority of human tumors, and the ability of E2F-1 to inhibit antiapoptotic signaling may contribute to the enhanced sensitivity of transformed cells to chemotherapeutic agents.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Apoptosis* / drug effects
  • Carrier Proteins*
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Cycle Proteins*
  • Cell Line
  • DNA / biosynthesis
  • DNA-Binding Proteins*
  • Down-Regulation
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • Gene Expression
  • Humans
  • I-kappa B Kinase
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • Mitogen-Activated Protein Kinases / metabolism
  • Mutation / genetics
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / chemistry
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Protein-Serine-Threonine Kinases / antagonists & inhibitors
  • Protein-Serine-Threonine Kinases / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Receptors, Tumor Necrosis Factor / drug effects
  • Receptors, Tumor Necrosis Factor / metabolism
  • Retinoblastoma Protein / genetics
  • Retinoblastoma Protein / metabolism
  • Retinoblastoma-Binding Protein 1
  • S Phase
  • Signal Transduction* / drug effects
  • TNF Receptor-Associated Factor 2
  • Transcription Factor DP1
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Tumor Necrosis Factor-alpha / pharmacology
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / physiology

Substances

  • Arid4a protein, mouse
  • Carrier Proteins
  • Caspase Inhibitors
  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • E2F Transcription Factors
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • E2f1 protein, mouse
  • NF-kappa B
  • Proteins
  • Receptors, Tumor Necrosis Factor
  • Retinoblastoma Protein
  • Retinoblastoma-Binding Protein 1
  • TNF Receptor-Associated Factor 2
  • Transcription Factor DP1
  • Transcription Factors
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • DNA
  • Protein-Serine-Threonine Kinases
  • CHUK protein, human
  • Chuk protein, mouse
  • I-kappa B Kinase
  • IKBKB protein, human
  • IKBKE protein, human
  • Ikbkb protein, mouse
  • Ikbke protein, mouse
  • JNK Mitogen-Activated Protein Kinases
  • Mitogen-Activated Protein Kinases
  • Caspases