title: Daxx-beta and Daxx-gamma, two novel splice variants of the transcriptional co-repressor Daxx.
abstract: Daxx is involved in transcriptional control and apoptosis. It comprises several domains, including a regulatory C terminus that is responsible for the interaction with numerous proteins such as p53, promyelocytic leukemia protein (PML), and Hsp27. Here, we describe the identification and characterization of two novel variants of Daxx termed Daxx-β and Daxx-γ, which are generated by alternative splicing. Alternative splicing results in a truncated regulatory C terminus in both proteins. As a consequence, Daxx-β and Daxx-γ show a markedly decreased affinity to PML, which in turn is associated with a different subnuclear localization of these proteins compared with Daxx. Although Daxx is localized mainly in PML-oncogenic domains (PODs) Daxx-β and Daxx-γ display a distinct distribution pattern. Furthermore, Daxx-β and Daxx-γ show a decreased affinity to p53 also due to the truncated C terminus. We provide evidence that the p53 recruitment into PODs is Daxx isoform-dependent. The decreased affinity of Daxx-β/-γ to p53 and PML results in a diffuse localization of p53 throughout the nucleus. In contrast to Daxx, Daxx-β and Daxx-γ are unable to repress p53-mediated transcription. Therefore, alternative splicing of Daxx might indicate an additional level in the cellular apoptosis network.
authors.affiliation: Institute of Pathology, Heinrich Heine University, University Hospital, Medical Faculty, Düsseldorf, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Wethkamp
authors.forename: Helmut
authors.initials: H
authors.lastname: Hanenberg
authors.forename: Sarah
authors.initials: S
authors.lastname: Funke
authors.forename: Christoph V
authors.initials: CV
authors.lastname: Suschek
authors.forename: Wiebke
authors.initials: W
authors.lastname: Wetzel
authors.forename: Sebastian
authors.initials: S
authors.lastname: Heikaus
authors.forename: Edgar
authors.initials: E
authors.lastname: Grinstein
authors.forename: Uwe
authors.initials: U
authors.lastname: Ramp
authors.forename: Rainer
authors.initials: R
authors.lastname: Engers
authors.forename: Helmut E
authors.initials: HE
authors.lastname: Gabbert
authors.forename: Csaba
authors.initials: C
authors.lastname: Mahotka
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000235:genetics; D017398:Alternative Splicing / Q000502:physiology*; D017209:Apoptosis / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism*; D056970:Co-Repressor Proteins; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018832:Molecular Chaperones; D009687:Nuclear Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms / Q000096:biosynthesis / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000096:biosynthesis* / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins; D000071156:Promyelocytic Leukemia Protein; D020033:Protein Isoforms; D012097:Repressor Proteins; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; C070576:PML protein, human