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dc.contributor.authorTenbaum, Stephan
dc.date.accessioned2023-03-03T14:40:17Z
dc.date.available2002-09-08T22:00:00Z
dc.date.available2023-03-03T14:40:17Z
dc.date.issued2002
dc.identifier.urihttp://nbn-resolving.de/urn:nbn:de:hebis:26-opus-8111
dc.identifier.urihttps://jlupub.ub.uni-giessen.de//handle/jlupub/10563
dc.identifier.urihttp://dx.doi.org/10.22029/jlupub-9946
dc.description.abstractAlien protein isoforms have been described to be involved in a number of biological processes. Alienalpha is a corepressor of the thyroidhormone receptor mediating transcriptional repression in a ligand-sensitive manner. Furthermore, Alienalpha is a corepressor for theorphan receptor DAX1 and the vitamin-D3 receptor. Alienbetta/CSN2 is part of the COP9-signalosome complex that acts in proteinphosphorylation, protein degradation and cell cycle regulation. The major goal of this work was to characterize the Alienalpha and Alienbetta isoforms. Little was known about their expression pattern andthe regulation of their expression had not been addressed. It was determined in this work that the expression pattern of Alien is rather ubiquitous in rat tissues. Interestingly, a putative novel Alienprotein isoform and an additional alien messenger specific for adrenal gland were identified. Furthermore, it was shown in vivo and in vitro,by in situ hybridization, Northern and Western blotting that Alien expression is regulated by thyroid hormone in the rat brain andbrain-derived cell lines. Subsequently, hints for a second T3-independent mechanism of regulation of Alien expression depending on cellconfluence or quiescence were discovered. The comparison of Alien isoforms in functional aspects identified Rb and E2F as novel Alien-interacting proteins with similar bindingcharacteristics in vitro and in yeast but functional differences in vivo. Alienbetta interfered with Rb-mediated superactivation of Sp1-driventranscription, whereas Aliena exerted strong repression on E2F transactivation. Common traits for both Alienalpha and Alienbetta are theirsilencing potential, interaction with TR and activation of AP1-driven transcription. Phosphorylation studies raised the possibility of regulation by non-hormonal signaling since Alienalpha and Alienbetta are phosphorylatedin vivo. In gel kinase assays suggested the existence of two different Alien-phosphorylating kinases. Further experiments identified MLK2and the cell cycle kinase p34cdc2 as such kinases, suggesting a possible function of Alien in cell cycle regulation. Taken together, the expression of Alien is regulated by thyroid hormone, and by cell density; the isoforms can be phosphorylated and canact either as transcriptional repressors or as activators. Additional data indicate a role of Alien isoforms in cell cycle regulation throughp34cdc2 phosphorylation and isoform-specific interference with Rb and E2F.en
dc.language.isoende_DE
dc.rightsIn Copyright*
dc.rights.urihttp://rightsstatements.org/page/InC/1.0/*
dc.subject.ddcddc:570de_DE
dc.titleCharacterization of Alien isoforms in vertebrates : Caracterización de isoformas de Alien en vertebradosen
dc.title.alternativeCharakterisierung von Alien Isoformen in Vertebratende_DE
dc.typedoctoralThesisde_DE
dcterms.dateAccepted2002-08-19
local.affiliationFB 08 - Biologie und Chemiede_DE
thesis.levelthesis.doctoralde_DE
local.opus.id811
local.opus.instituteGenetisches Institut und Instituto des Investigaciones Biomedicas, Consejo Superior de Investigaciones Cientificas (CSIC), Universidad Autonoma de Madridde_DE
local.opus.fachgebietBiologiede_DE


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