Identification of hTAF(II)80 delta links apoptotic signaling pathways to transcription factor TFIID function

Mol Cell. 2001 Sep;8(3):591-600. doi: 10.1016/s1097-2765(01)00325-2.

Abstract

Apoptotic cell death is associated with altered levels of mRNA expression, yet the mechanisms that coordinate changes in gene expression with activation of the cell death machinery remain obscure. Here, we report the cloning and characterization of hTAF(II)80 delta, a specialized isoform of the general transcription factor TFIID subunit hTAF(II)80. Several distinct apoptotic stimuli induce the expression and caspase-dependent cleavage of hTAF(II)80 delta. hTAF(II)80 delta, unlike hTAF(II)80, forms a TFIID-like complex lacking hTAF(II)31. Elevated expression of hTAF(II)80 delta in HeLa cells is sufficient to trigger apoptotic cell death and selectively alters cellular transcription, including the induction of the target genes gadd45 and p21. These data define a signaling pathway that couples apoptotic signals to a reprogramming of RNA polymerase II transcription.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Apoptosis / drug effects
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins
  • Camptothecin / pharmacology
  • Caspase Inhibitors
  • Caspases / metabolism
  • Cell Line
  • Cloning, Molecular
  • Enzyme Inhibitors / pharmacology
  • Etoposide / pharmacology
  • GADD45 Proteins
  • Humans
  • Immunoblotting
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Membrane Glycoproteins / metabolism
  • Molecular Sequence Data
  • Nucleic Acid Synthesis Inhibitors / pharmacology
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Protein Isoforms / genetics
  • Protein Isoforms / metabolism
  • Proteins / genetics
  • Proteins / metabolism
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction / physiology*
  • Staurosporine / pharmacology
  • TATA-Binding Protein Associated Factors
  • TNF-Related Apoptosis-Inducing Ligand
  • Transcription Factor TFIID
  • Transcription Factors / chemistry
  • Transcription Factors / genetics
  • Transcription Factors / metabolism*
  • Transcription Factors, TFII / genetics
  • Transcription Factors, TFII / metabolism*
  • Transcription, Genetic / physiology
  • Tumor Necrosis Factor-alpha / metabolism
  • rho GTP-Binding Proteins / genetics
  • rho GTP-Binding Proteins / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Caspase Inhibitors
  • Enzyme Inhibitors
  • Intracellular Signaling Peptides and Proteins
  • Macromolecular Substances
  • Membrane Glycoproteins
  • Nucleic Acid Synthesis Inhibitors
  • Protein Isoforms
  • Proteins
  • Recombinant Fusion Proteins
  • TAF6 protein, human
  • TATA-Binding Protein Associated Factors
  • TNF-Related Apoptosis-Inducing Ligand
  • TNFSF10 protein, human
  • Transcription Factor TFIID
  • Transcription Factors
  • Transcription Factors, TFII
  • Tumor Necrosis Factor-alpha
  • Etoposide
  • PARP1 protein, human
  • Poly (ADP-Ribose) Polymerase-1
  • Poly(ADP-ribose) Polymerases
  • Caspases
  • rho GTP-Binding Proteins
  • Staurosporine
  • Camptothecin