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The cell type-specific effect of TAp73 isoforms on the cell cycle and apoptosis

Abstract

p73, a member of the p53 family, exhibits activities similar to those of p53, including the ability to induce growth arrest and apoptosis. p73 influences chemotherapeutic responses in human cancer patients, in association with p53. Alternative splicing of the TP73 gene produces many p73 C- and N-terminal isoforms, which vary in their transcriptional activity towards p53-responsive promoters. In this paper, we show that the C-terminal spliced isoforms of the p73 protein differ in their DNA-binding capacity, but this is not an accurate predictor of transcriptional activity. In different p53-null cell lines, p73β induces either mitochondrial-associated or death receptor-mediated apoptosis, and these differences are reflected in different gene expression profiles. In addition, p73 induces cell cycle arrest and p21WAF1 expression in H1299 cells, but not in Saos-2. This data shows that TAp73 isoforms act differently depending on the tumour cell background, and have important implications for p73-mediated therapeutic responses in individual human cancer patients.

Abbreviations

ADO22:

TRAF and TNF receptor-associated protein-22

APEX:

apurinic/apyrimidinic endonuclease 1/redox factor

ASPP2:

apoptosis stimulating proteins of p53

CDK1(cdc2):

cyclin-dependent protein kinase-1

D-MEM:

Dulbecco's modified Eagle medium

DR5:

trail death receptor

EMSA:

electrophoretic mobility-shift assay

FAF1:

Fas-associated factor

FBS:

foetal bovine serum

IVTT:

in vitro transcription/translation

MAP4:

microtubule-associated protein 4

PIDD:

p53-induced protein with a death domain

PML:

promyelocytic leukaemia gene

SDS-PAGE:

SDS-polyacrylamide gel electrophoresis

TRAFs:

TNF receptor-associated factor

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Correspondence to Borivoj Vojtesek.

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These authors contributed equally to this paper

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Holcakova, J., Ceskova, P., Hrstka, R. et al. The cell type-specific effect of TAp73 isoforms on the cell cycle and apoptosis. Cell Mol Biol Lett 13, 404–420 (2008). https://doi.org/10.2478/s11658-008-0011-z

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  • DOI: https://doi.org/10.2478/s11658-008-0011-z

Key words

  • p53
  • TAp73
  • ΔTAp73
  • DNA binding
  • Transactivation
  • Cell cycle
  • Apoptosis