Researcher:
Köken, Ayşe Nur Polat

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Master Student

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Ayşe Nur Polat

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Köken

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Köken, Ayşe Nur Polat

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2014 - 20194

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    Phosphoproteomic analysis of aurora kinase inhibition in monopolar cytokinesis
    (Amer Chemical Soc, 2015) Giese, Sven H.; Hu, Chi-Kuo; Renard, Bernhard Y.; N/A; N/A; N/A; N/A; Department of Molecular Biology and Genetics; Köken, Ayşe Nur Polat; Karayel, Özge; Harmanda, Büşra; Şanal, Erdem; Master Student; Master Student; Researcher; Master Student; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; College of Sciences; 239008; N/A; N/A; N/A; 105301
    Cytokinesis is the last step of the cell cycle that requires coordinated activities of the microtubule c-ytoskeleton, actin cytoskeleton, and membrane compartments. Aurora B kinase is one of the master regulatory kinases that orchestrate multiple events during cytokinesis. To reveal targets of the Aurora B kinase, we combined quantitative mass spectrometry with chemical genetics. Using the quantitative proteomic approach, SILAC (stable isotope labeling with amino acids in cell culture), we analyzed the phosphoproteome of monopolar cytokinesis upon VX680- or AZD1152-mediated aurora kinase inhibition. In total, our analysis quantified over 20 000 phosphopeptides in response to the Aurora-B kinase inhibition; 246 unique phosphopeptides were significantly down-regulated and 74 were up-regulated. Our data provide a broad analysis of downstream effectors of Aurora kinase and offer insights into how Aurora kinase regulates cytokinesis.
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    Systems-level analysis reveals multiple modulators of epithelial-mesenchymal transition and identifies DNAJB4 and CD81 as novel metastasis inducers in breast cancer
    (American Society Biochemistry Molecular Biology, 2019) Saatci, Ozge; Ersan, Pelin Gulizar; Trappe, Kathrin; Renard, Bernhard Y.; Tuncbag, Nurcan; Sahin, Ozgur; Department of Molecular Biology and Genetics; N/A; N/A; Önder, Tamer Tevfik; Kagiali, Zeynep Cansu Üretmen; Şanal, Erdem; Karayel, Özge; Köken, Ayşe Nur Polat; Sıcakkan, Nurhan Özlü; Faculty Member; Faculty Member; PhD Student; PhD Student; Master Student; Master Student; Department of Molecular Biology and Genetics; Koç University Research Center for Translational Medicine (KUTTAM) / Koç Üniversitesi Translasyonel Tıp Araştırma Merkezi (KUTTAM); College of Sciences; School of Medicine; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; Graduate School of Sciences and Engineering; 105301; 42946; N/A; N/A; N/A; N/A
    Epithelial-mesenchymal transition (EMT) is driven by complex signaling events that induce dramatic biochemical and morphological changes whereby epithelial cells are converted into cancer cells. However, the underlying molecular mechanisms remain elusive. Here, we used mass spectrometry based quantitative proteomics approach to systematically analyze the post-translational biochemical changes that drive differentiation of human mammary epithelial (HMLE) cells into mesenchymal. We identified 314 proteins out of more than 6,000 unique proteins and 871 phosphopeptides out of more than 7,000 unique phosphopeptides as differentially regulated. We found that phosphoproteome is more unstable and prone to changes during EMT compared with the proteome and multiple alterations at proteome level are not thoroughly represented by transcriptional data highlighting the necessity of proteome level analysis. We discovered cell state specific signaling pathways, such as Hippo, sphingolipid signaling, and unfolded protein response (UPR) by modeling the networks of regulated proteins and potential kinase-substrate groups. We identified two novel factors for EMT whose expression increased on EMT induction: DnaJ heat shock protein family (Hsp40) member B4 (DNAJB4) and cluster of differentiation 81 (CD81). Suppression of DNAJB4 or CD81 in mesenchymal breast cancer cells resulted in decreased cell migration in vitro and led to reduced primary tumor growth, extravasation, and lung metastasis in vivo. Overall, we performed the global proteomic and phosphoproteomic analyses of EMT, identified and validated new mRNA and/ or protein level modulators of EMT. This work also provides a unique platform and resource for future studies focusing on metastasis and drug resistance.
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    PublicationOpen Access
    Comparative phosphoproteomic analysis reveals signaling networks regulating monopolar and bipolar cytokinesis
    (Nature Publishing Group (NPG), 2018) Department of Molecular Biology and Genetics; Karayel, Özge; Şanal, Erdem; Kagiali, Zeynep Cansu Üretmen; Köken, Ayşe Nur Polat; Faculty Member; Department of Molecular Biology and Genetics; Graduate School of Sciences and Engineering; N/A; N/A; N/A; N/A; 105301
    The successful completion of cytokinesis requires the coordinated activities of diverse cellular components including membranes, cytoskeletal elements and chromosomes that together form partly redundant pathways, depending on the cell type. The biochemical analysis of this process is challenging due to its dynamic and rapid nature. Here, we systematically compared monopolar and bipolar cytokinesis and demonstrated that monopolar cytokinesis is a good surrogate for cytokinesis and it is a well-suited system for global biochemical analysis in mammalian cells. Based on this, we established a phosphoproteomic signature of cytokinesis. More than 10,000 phosphorylation sites were systematically monitored; around 800 of those were up-regulated during cytokinesis. Reconstructing the kinase-substrate interaction network revealed 31 potentially active kinases during cytokinesis. The kinase-substrate network connects proteins between cytoskeleton, membrane and cell cycle machinery. We also found consensus motifs of phosphorylation sites that can serve as biochemical markers specific to cytokinesis. Beyond the kinase-substrate network, our reconstructed signaling network suggests that combination of sumoylation and phosphorylation may regulate monopolar cytokinesis specific signaling pathways. Our analysis provides a systematic approach to the comparison of different cytokinesis types to reveal alternative ways and a global overview, in which conserved genes work together and organize chromatin and cytoplasm during cytokinesis.
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    PublicationOpen Access
    Towards single-cell LC-MS phosphoproteomics
    (Royal Society of Chemistry (RSC), 2014) Department of Molecular Biology and Genetics; Köken, Ayşe Nur Polat; Faculty Member; Department of Molecular Biology and Genetics; College of Sciences; N/A; 105301
    Protein phosphorylation is a ubiquitous posttranslational modification, which is heavily involved in signal transduction. Misregulation of protein phosphorylation is often associated with a decrease in cell viability and complex diseases such as cancer. The dynamic and low abundant nature of phosphorylated proteins makes studying phosphoproteome a challenging task. In this review, we summarize state of the art proteomic techniques to study and quantify peptide phosphorylation in biological systems and discuss their limitations. Due to its short-lived nature, the phosphorylation event cannot be precisely traced in a heterogonous cell population, which highlights the importance of analyzing phosphorylation events at the single cell level. Mainly, we focus on the methodical and instrumental developments in proteomics and nanotechnology, which will help to build more accurate and robust systems for the feasibility of phosphorylation analysis at the single cell level. We propose that an automated and miniaturized construction of analytical systems holds the key to the future of phosphoproteomics; therefore, we highlight the benchmark studies in this direction. Having advanced and automated microfluidic chip LC systems will allow us to analyze single-cell phosphoproteomics and quantitatively compare it with others. The progress in the microfluidic chip LC systems and feasibility of the single-cell phosphoproteomics will be beneficial for early diagnosis and detection of the treatment response of many crucial diseases.