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.
MeSH Terms
Amino Acid Sequence
Apoptosis/drug effects,physiology
Apoptosis Regulatory Proteins
Camptothecin/pharmacology
Caspase Inhibitors
Caspases/metabolism
Cell Line
Cloning, Molecular
Enzyme Inhibitors/pharmacology
Etoposide/pharmacology
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,metabolism
Proteins/genetics,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,genetics,metabolism
Transcription Factors, TFII/genetics,metabolism
Transcription, Genetic/physiology
Tumor Necrosis Factor-alpha/metabolism
rho GTP-Binding Proteins/genetics,metabolism
Chemicals
Apoptosis Regulatory Proteins
Caspase Inhibitors
Enzyme Inhibitors
GADD45 protein
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
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Bell B
Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, BP 163, F-67404 ILLKIRCH Cedex, C.U. de Strasbourg, France.
Scheer E
Tora L