Dokument: Functional characterization of Drosophila sturkopf in cell proliferation and endocrine physiology regulation
| Titel: | Functional characterization of Drosophila sturkopf in cell proliferation and endocrine physiology regulation | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=64305 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20240301-081013-8 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Akhtar, Irfan [Autor] | |||||||
| Dateien: |
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| Beitragende: | Jun.-Prof. Dr. Beller, Mathias [Gutachter] Prof. Dr. Klein, Thomas [Gutachter] | |||||||
| Dewey Dezimal-Klassifikation: | 500 Naturwissenschaften und Mathematik » 570 Biowissenschaften; Biologie | |||||||
| Beschreibung: | Lipid droplets (LDs) are highly dynamic organelles involved in many physiological and pathophysiological processes. Especially the LD-associated proteome affects health and disease. Deregulation of lipid droplet associated proteins (LDAPs) is linked to obesity, diabetes, and several types of cancer, including prostate cancer
(PCa). The LDAP protein LDAH (lipid droplet-associated hydrolase) and its homologs were shown to impact a broad spectrum of physiological processes including cell proliferation and endocrine regulation. Loss of LDAH promotes PCa in mice and humans. The molecular mechanism of how LDAH loss of function (LOF) promotes prostate carcinogenesis is, however, not understood. The aim of this study was, hence, to investigate whether the function of the Drosophila LDAH homolog sturkopf affects proliferation and endocrine physiology regulation in vitro and in vivo. The results of cell proliferation assays in cultured Drosophila cells confirm a role of sturkopf on cell proliferation. Protein-protein interaction (PPI) studies suggest that sturkopf participates in the regulation of protein stability and the ubiquitination machinery. Deregulation of androgen signaling is a hallmark of PCa. Regulation of ecdysone signaling in the accessory gland (AG), the functional analog of the mammalian prostate, and androgen signaling in the prostate were shown to partially underly conserved mechanisms. A deregulation of ecdysone signaling in sturkopf mutant males was hypothesized previously. In vitro and in vivo analyses of a putative sturkopf-mediated regulation of ecdysone signaling indicate a stabilizing role of sturkopf in EcR protein stability. Significantly reduced ecdysone hemolymph titers in male sturkopf LOF animals signify a profound role of sturkopf in ecdysone signaling. Moreover, in vivo analyses of sturkopf LOF animals revealed a remarkable loss of secondary cells (SCs) in the AG in a sturkopf- and likely SC-dependent manner. Data of this work further proposes alterations in apoptotic processes in sturkopf LOF animals causing the loss of SCs. Cell survival and proliferation due to loss of apoptosis promotes tumorigenesis ultimately leading to PCa. Altogether, the results of this work reveal a crucial role of sturkopf in proliferation, endocrine physiology regulation, as well as protein stability regulation. As all these aspects have a high significance in PCa, the study aids in gaining a mechanistic insight of LDAH loss and prostate carcinogenesis in the mammalian system. | |||||||
| Lizenz: |  Dieses Werk ist lizenziert unter einer Creative Commons Namensnennung 4.0 International Lizenz | |||||||
| Fachbereich / Einrichtung: | Mathematisch- Naturwissenschaftliche Fakultät | |||||||
| Dokument erstellt am: | 01.03.2024 | |||||||
| Dateien geändert am: | 01.03.2024 | |||||||
| Promotionsantrag am: | 15.03.2023 | |||||||
| Datum der Promotion: | 31.10.2023 |
