TR-Dizin İndeksli Yayınlar Koleksiyonu
Permanent URI for this collectionhttps://hdl.handle.net/20.500.12573/396
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Article Citation - WoS: 1Citation - Scopus: 1RPI-1 (Human DCDC2) Displays Functional Redundancy With Nephronophthisis 4 in Regulating Cilia Biogenesis in C. Elegans(Tubitak Scientific & Technological Research Council Turkey, 2023-01-01) Kaplan, Oktay I.Projecting from most cell surfaces, cilia serve as important hubs for sensory and signaling processes and have been linked to a variety of human disorders, including Bardet-Biedl Syndrome (BBS), Meckel-Gruber Syndrome (MKS), Nephronophthisis (NPHP), and Joubert Syndrome, and these diseases are collectively known as a ciliopathy. DCDC2 is a ciliopathy protein that localizes to cilia; nevertheless, our understanding of the role of DCDC2 in cilia is still limited. We employed C. elegans to investigate the function of C. elegans RPI-1, a Caenorhabditis elegans ortholog of human DCDC2, in cilia and found that C. elegans RPI-1 localizes to the entire ciliary axoneme, but is not present in the transition zone and basal body. We generated a null mutant of C. elegans rpi-1, and our analysis with a range of fluorescence-based ciliary markers revealed that DCDC2 and nephronophthisis 4 (NPHP-4/NPHP4) display functional redundant roles in regulating cilia length and cilia positions. Taken together, our analysis discovered a novel genetic interaction between two ciliopathy disease genes (RPI-1/DCDC2 and NPHP-4/NPHP4) in C. elegans.Article Investigating the Impact of Birt–hogg–dubé Syndrome Associated Folliculin (Flcn) and Retinitis Pigmentosa 2 (Rp2) Loss on Cilia Function and Morphology(2024-06-30) Kaplan, Oktay IsmailFolliculin (FLCN), a GTPase-activating protein (GAP), has been linked to Birt–Hogg–Dubé syndrome, the mTORC1 signaling pathway and cilia. Disruptions in cilia structure and function lead to a group of diseases known as ciliopathies. Birt-Hogg-Dubé syndrome is one of 35 different ciliopathy diseases and there are more than 250 genes that cause ciliopathy diseases. FLCN interacts with kinesin-2 along cilia. The specific role of FLCN in regulating Kinesin-IFT trafficking has, however, remained unclear. In the current study, we investigated the effects of flcn-1 loss (the human ortholog of FLCN) on kinesin and IFT trafficking in C. elegans. The loss of flcn-1 alone did not result in any apparent alterations to kinesin or IFT trafficking within the cilia. However, when we combined the deletion of flcn-1 with the deletion of Retinitis Pigmentosa 2 (RP2), another GAP protein, the ciliary entry of a non-ciliary membrane protein TRAM-1 (Translocation Associated Membrane Protein 1) occured. Additionally, although cilia length was unaltered, our analysis of double mutants revealed the extra branch in wing AWB cilia morphology but not the single rod-like PHA/PHB cilia. In summary, our study reveals the previously unknown functions of FLCN in ciliary gating and cilia morphology in C. elegansArticle Cytotoxic and Cytostatic Effects of Targeting mTOR and Hedgehog Pathways in Acute Myeloid Leukemia(Istanbul Univ, 2022-12-29) Cicek, Enes; Kucuktas, Fulya Mina; Yenigul, Munevver; Akcok, Emel Basak GencerObjectives: Acute myeloid leukemia (AML) is a highly aggressive heterogeneous hematopoietic malignancy characterized by a rapid and abnormal proliferation of immature myeloid leukemia cells in the bone marrow and peripheral blood. Aberrant alterations in signal transduction pathways are strongly associated with the progression of AML. This study aimed to investigate cell viability and the cell cycle in AML cells by targeting the Hedgehog and mTOR signaling pathways with rapamycin and GANT61. Materials and Method: The antiproliferative effect of rapamycin and GANT61 was assessed by the MTT cell viability assay in two AML cell lines: CMK and MOLM-13. The effect of the inhibitors on cell-cycle distribution was determined using propidium iodide staining and measured with flow cytometry. Results: Rapamycin, an mTOR inhibitor, and GANT61, a Gli-1 inhibitor, decreased the cell proliferation of CMK and MOLM-13 cells. The IC20 values, which is the drug concentration that inhibits cell growth by 20%, were combined and administered to the cells. The results show the drugs to have a combinatorial inhibitory effect on CMK cells but not on MOLM-13 cells. In addition, the combination of drugs arrested the cells during the G0/G1 phase. Conclusion: This study suggests a novel combination therapy approach for AML via mTOR and Hedgehog signaling pathway inhibition using rapamycin and GANT61, respectively. It also suggest further studies be performed to reveal the mechanism of action.Article Aurora Kinases: Their Role in Cancer and Cellular Processes(2024-06-28) Sarı, Sıbel; Özsoy, Elif RumeysaAurora kinazlar, Aurora A, B ve C şeklinde tanımlanan üç üyeye sahip, hücre döngüsünün düzenlenmesinde kritik rolleri olan yüksek oranda korunmuş serin/treonin kinaz ailesine ait proteinlerdir. Aurora kinazlar, kromozom stabilitesinin korunmasında önemli rolleri olan mitotik düzenleyiciler olarak hizmet etmektedir. Mitozdaki çeşitli olaylarda kritik roller üstlenen Aurora kinazlar, kromozomal ve sitoskeletal olayların koordinasyonu, iğ ipliği oluşumu kontrolü ve sitokinez gibi olaylarda görev alarak hücre döngüsünün sorunsuz ilerlemesini sağlamaktadır. Mitotik fonksiyonlarının yanı sıra, Aurora kinazlar mayoz bölünmenin düzenlenmesi süreçlerinde de yer almaktadırlar. Aurora kinazların gen amplifikasyonu/mutasyonu ve aşırı ifadesi çeşitli solid ve hematolojik kanserlerde tespit edilmiştir. Aurora kinazlar mitotik rolleri ile ilişkilendirilen onkojenik fonksiyonları ile kanser hücrelerinin çoğalması ve hayatta kalmalarını sağlamaktadırlar. Aurora kinaz aktivitesinin bozulması, sentrozom fonksiyonunda, iğ ipliklerinin oluşumunda, kromozomal hizalanmada ve sitokinezde sorunlara neden olarak mitotik anormallikler ve genetik istikrarsızlığa yol açmaktadır. Bu bulgular, Aurora kinazların kanserdeki önemli fonksiyonlarını vurgulayarak kanser terapötikleri için değerli hedefler olarak tanınmalarını sağlamaktadır. Bu derleme, Aurora kinazların yapı ve fonksiyonlarına genel bir bakış sunarak, bu kinazların kanserdeki onkojenik rollerini aydınlatmaktadır.