title: Analysis of the oligomeric state and transactivation potential of TAp73α.
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.
authors.affiliation: Institute of Biophysical Chemistry and Center for Biomolecular Magnetic Resonance, Goethe University, Frankfurt, Germany.
authors.forename: L M
authors.initials: LM
authors.lastname: Luh
authors.forename: S
authors.initials: S
authors.lastname: Kehrloesser
authors.forename: G B
authors.initials: GB
authors.lastname: Deutsch
authors.forename: J
authors.initials: J
authors.lastname: Gebel
authors.forename: D
authors.initials: D
authors.lastname: Coutandin
authors.forename: B
authors.initials: B
authors.lastname: Schäfer
authors.forename: M
authors.initials: M
authors.lastname: Agostini
authors.forename: G
authors.initials: G
authors.lastname: Melino
authors.forename: V
authors.initials: V
authors.lastname: Dötsch
mesh_terms: D000595:Amino Acid Sequence; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000032:analysis / Q000737:chemistry* / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000032:analysis / Q000737:chemistry* / Q000502:physiology*; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs / Q000502:physiology*; D020033:Protein Isoforms / Q000032:analysis / Q000737:chemistry / Q000502:physiology; D015533:Transcriptional Activation / Q000502:physiology*; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins / Q000032:analysis / Q000737:chemistry* / Q000502:physiology*
chemical_list: C081876:CKAP4 protein, human; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D009687:Nuclear Proteins; D020033:Protein Isoforms; C000606460:TP73 protein, human; D000072160:Tumor Protein p73; D025521:Tumor Suppressor Proteins
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