Analysis of the oligomeric state and transactivation potential of TAp73α

L. M. Luh, S. Kehrloesser, G. B. Deutsch, J. Gebel, D. Coutandin, B. Schäfer, M. Agostini, G. Melino, V. Dötsch

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

The proteins p73 and p63 are members of the p53 protein family and are involved in important developmental processes. Their high sequence identity with the tumor suppressor p53 has suggested that they act as tumor suppressors as well. While p63 has a crucial role in the maintenance of epithelial stem cells and in the quality control of oocytes without a clear role as a tumor suppressor, p73's tumor suppressor activity is well documented. In a recent study we have shown that the transcriptional activity of TAp63α, the isoform responsible for the quality control in oocytes, is regulated by its oligomeric state. The protein forms an inactive, dimeric and compact conformation in resting oocytes, while the detection of DNA damage leads to the formation of an active, tetrameric and open conformation. p73 shows a high sequence identity to p63, including those domains that are crucial in stabilizing its inactive state, thus suggesting that p73's activity might be regulated by its oligomeric state as well. Here, we have investigated the oligomeric state of TAp73α by size exclusion chromatography and detailed domain interaction mapping, and show that in contrast to p63, TAp73α is a constitutive open tetramer. However, its transactivation potential depends on the cellular background and the promoter context. These results imply that the regulation of p73's transcriptional activity might be more closely related to p53 than to p63.

Original languageEnglish
Pages (from-to)1008-1016
Number of pages9
JournalCell Death and Differentiation
Volume20
Issue number8
DOIs
Publication statusPublished - Aug 2013

Fingerprint

Transcriptional Activation
Oocytes
Quality Control
Neoplasms
DNA Damage
Gel Chromatography
Protein Isoforms
Proteins
Stem Cells
Epithelial Cells
Maintenance

Keywords

  • p53 family
  • p63
  • p73
  • Tetramerization
  • Transcriptional activity

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Luh, L. M., Kehrloesser, S., Deutsch, G. B., Gebel, J., Coutandin, D., Schäfer, B., ... Dötsch, V. (2013). Analysis of the oligomeric state and transactivation potential of TAp73α. Cell Death and Differentiation, 20(8), 1008-1016. https://doi.org/10.1038/cdd.2013.23

Analysis of the oligomeric state and transactivation potential of TAp73α. / Luh, L. M.; Kehrloesser, S.; Deutsch, G. B.; Gebel, J.; Coutandin, D.; Schäfer, B.; Agostini, M.; Melino, G.; Dötsch, V.

In: Cell Death and Differentiation, Vol. 20, No. 8, 08.2013, p. 1008-1016.

Research output: Contribution to journalArticle

Luh, LM, Kehrloesser, S, Deutsch, GB, Gebel, J, Coutandin, D, Schäfer, B, Agostini, M, Melino, G & Dötsch, V 2013, 'Analysis of the oligomeric state and transactivation potential of TAp73α', Cell Death and Differentiation, vol. 20, no. 8, pp. 1008-1016. https://doi.org/10.1038/cdd.2013.23
Luh LM, Kehrloesser S, Deutsch GB, Gebel J, Coutandin D, Schäfer B et al. Analysis of the oligomeric state and transactivation potential of TAp73α. Cell Death and Differentiation. 2013 Aug;20(8):1008-1016. https://doi.org/10.1038/cdd.2013.23
Luh, L. M. ; Kehrloesser, S. ; Deutsch, G. B. ; Gebel, J. ; Coutandin, D. ; Schäfer, B. ; Agostini, M. ; Melino, G. ; Dötsch, V. / Analysis of the oligomeric state and transactivation potential of TAp73α. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 8. pp. 1008-1016.
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