12 results on '"Karakaya, Tugay"'
Search Results
2. CARD8: A Novel Inflammasome Sensor with Well-Known Anti-Inflammatory and Anti-Apoptotic Activity.
- Author
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Karakaya, Tugay, Slaufova, Marta, Di Filippo, Michela, Hennig, Paulina, Kündig, Thomas, and Beer, Hans-Dietmar
- Subjects
- *
INFLAMMASOMES , *NF-kappa B , *ANTI-inflammatory agents , *ALTERNATIVE RNA splicing , *SINGLE nucleotide polymorphisms , *PEPTIDASE - Abstract
Inflammasomes comprise a group of protein complexes with fundamental roles in the induction of inflammation. Upon sensing stress factors, their assembly induces the activation and release of the pro-inflammatory cytokines interleukin (IL)-1β and -18 and a lytic type of cell death, termed pyroptosis. Recently, CARD8 has joined the group of inflammasome sensors. The carboxy-terminal part of CARD8, consisting of a function-to-find-domain (FIIND) and a caspase activation and recruitment domain (CARD), resembles that of NLR family pyrin domain containing 1 (NLRP1), which is recognized as the main inflammasome sensor in human keratinocytes. The interaction with dipeptidyl peptidases 8 and 9 (DPP8/9) represents an activation checkpoint for both sensors. CARD8 and NLRP1 are activated by viral protease activity targeting their amino-terminal region. However, CARD8 also has some unique features compared to the established inflammasome sensors. Activation of CARD8 occurs independently of the inflammasome adaptor protein apoptosis-associated speck-like protein containing a CARD (ASC), leading mainly to pyroptosis rather than the activation and secretion of pro-inflammatory cytokines. CARD8 was also shown to have anti-inflammatory and anti-apoptotic activity. It interacts with, and inhibits, several proteins involved in inflammation and cell death, such as the inflammasome sensor NLRP3, CARD-containing proteins caspase-1 and -9, nucleotide-binding oligomerization domain containing 2 (NOD2), or nuclear factor kappa B (NF-κB). Single nucleotide polymorphisms (SNPs) of CARD8, some of them occurring at high frequencies, are associated with various inflammatory diseases. The molecular mechanisms underlying the different pro- and anti-inflammatory activities of CARD8 are incompletely understood. Alternative splicing leads to the generation of multiple CARD8 protein isoforms. Although the functional properties of these isoforms are poorly characterized, there is evidence that suggests isoform-specific roles. The characterization of the functions of these isoforms, together with their cell- and disease-specific expression, might be the key to a better understanding of CARD8's different roles in inflammation and inflammatory diseases. [ABSTRACT FROM AUTHOR]
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- 2024
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3. The gasdermins: a pore-forming protein family expressed in the epidermis
- Author
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Slaufova, Marta, primary, Karakaya, Tugay, additional, Di Filippo, Michela, additional, Hennig, Paulina, additional, and Beer, Hans-Dietmar, additional
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- 2023
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4. The centrosome protein AKNA regulates neurogenesis via microtubule organization
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Camargo Ortega, Germán, Falk, Sven, Johansson, Pia A., Peyre, Elise, Broix, Loïc, Sahu, Sanjeeb Kumar, Hirst, William, Schlichthaerle, Thomas, De Juan Romero, Camino, Draganova, Kalina, Vinopal, Stanislav, Chinnappa, Kaviya, Gavranovic, Anna, Karakaya, Tugay, Steininger, Thomas, Merl-Pham, Juliane, Feederle, Regina, Shao, Wei, Shi, Song-Hai, Hauck, Stefanie M., Jungmann, Ralf, Bradke, Frank, Borrell, Victor, Geerlof, Arie, Reber, Simone, Tiwari, Vijay K., Huttner, Wieland B., Wilsch-Bräuninger, Michaela, Nguyen, Laurent, and Götz, Magdalena
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- 2019
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5. NLRP1 in Cutaneous SCCs: An Example of the Complex Roles of Inflammasomes in Cancer Development
- Author
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Di Filippo, Michela, Hennig, Paulina, Karakaya, Tugay, Slaufova, Marta, Beer, Hans-Dietmar, University of Zurich, and Beer, Hans-Dietmar
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1503 Catalysis ,1604 Inorganic Chemistry ,Organic Chemistry ,10177 Dermatology Clinic ,1607 Spectroscopy ,610 Medicine & health ,General Medicine ,Catalysis ,Computer Science Applications ,Inorganic Chemistry ,1312 Molecular Biology ,1706 Computer Science Applications ,Physical and Theoretical Chemistry ,1606 Physical and Theoretical Chemistry ,Molecular Biology ,Spectroscopy ,1605 Organic Chemistry - Published
- 2022
6. NLRP1 in Cutaneous SCCs: An Example of the Complex Roles of Inflammasomes in Cancer Development
- Author
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Di Filippo, Michela, primary, Hennig, Paulina, additional, Karakaya, Tugay, additional, Slaufova, Marta, additional, and Beer, Hans-Dietmar, additional
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- 2022
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7. NLRP1 Inflammasome Activation in Keratinocytes: Increasing Evidence of Important Roles in Inflammatory Skin Diseases and Immunity
- Author
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Fenini, Gabriele; https://orcid.org/0000-0002-5778-936X, Karakaya, Tugay; https://orcid.org/0000-0003-0683-579X, Hennig, Paulina; https://orcid.org/0000-0003-2633-452X, Di Filippo, Michela; https://orcid.org/0000-0002-3507-8639, Slaufova, Marta; https://orcid.org/0000-0002-9860-7390, Beer, Hans-Dietmar; https://orcid.org/0000-0002-8085-713X, Fenini, Gabriele; https://orcid.org/0000-0002-5778-936X, Karakaya, Tugay; https://orcid.org/0000-0003-0683-579X, Hennig, Paulina; https://orcid.org/0000-0003-2633-452X, Di Filippo, Michela; https://orcid.org/0000-0002-3507-8639, Slaufova, Marta; https://orcid.org/0000-0002-9860-7390, and Beer, Hans-Dietmar; https://orcid.org/0000-0002-8085-713X
- Abstract
In 2007, it was shown that DNA sequence variants of the human NLRP1 gene are associated with autoimmune and autoinflammatory diseases affecting mainly the skin. However, at that time, the underlying cellular and molecular mechanisms were poorly characterized. Meanwhile, increasing evidence suggests that the NLRP1 inflammasome expressed by keratinocytes not only plays a part in the pathology of common inflammatory skin diseases and cancer development but also contributes to skin immunity. Understanding the mechanisms regulating NLRP1 activation in keratinocytes and the downstream events in human skin might pave the way for developing novel strategies for treating patients suffering from NLRP1-mediated skin diseases.
- Published
- 2022
8. The Pathways Underlying the Multiple Roles of p62 in Inflammation and Cancer
- Author
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Hennig, Paulina, Fenini, Gabriele, Di Filippo, Michela, Karakaya, Tugay, and Beer, Hans-Dietmar
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autophagy ,inflammation ,QH301-705.5 ,p62 ,cancer ,Review ,Nrf2/Keap1 ,inflammasomes ,Biology (General) ,mTORC1 ,NF-κB - Abstract
p62 is a highly conserved, multi-domain, and multi-functional adaptor protein critically involved in several important cellular processes. Via its pronounced domain architecture, p62 binds to numerous interaction partners, thereby influencing key pathways that regulate tissue homeostasis, inflammation, and several common diseases including cancer. Via binding of ubiquitin chains, p62 acts in an anti-inflammatory manner as an adaptor for the auto-, xeno-, and mitophagy-dependent degradation of proteins, pathogens, and mitochondria. Furthermore, p62 is a negative regulator of inflammasome complexes. The transcription factor Nrf2 regulates expression of a bundle of ROS detoxifying genes. p62 activates Nrf2 by interaction with and autophagosomal degradation of the Nrf2 inhibitor Keap1. Moreover, p62 activates mTOR, the central kinase of the mTORC1 sensor complex that controls cell proliferation and differentiation. Through different mechanisms, p62 acts as a positive regulator of the transcription factor NF-κB, a central player in inflammation and cancer development. Therefore, p62 represents not only a cargo receptor for autophagy, but also a central signaling hub, linking several important pro- and anti-inflammatory pathways. This review aims to summarize knowledge about the molecular mechanisms underlying the roles of p62 in health and disease. In particular, different types of tumors are characterized by deregulated levels of p62. The elucidation of how p62 contributes to inflammation and cancer progression at the molecular level might promote the development of novel therapeutic strategies.
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- 2021
9. The NLRP1 inflammasome in human skin and beyond
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Fenini, Gabriele; https://orcid.org/0000-0002-5778-936X, Karakaya, Tugay, Hennig, Paulina; https://orcid.org/0000-0003-2633-452X, Di Filippo, Michela, Beer, Hans-Dietmar; https://orcid.org/0000-0002-8085-713X, Fenini, Gabriele; https://orcid.org/0000-0002-5778-936X, Karakaya, Tugay, Hennig, Paulina; https://orcid.org/0000-0003-2633-452X, Di Filippo, Michela, and Beer, Hans-Dietmar; https://orcid.org/0000-0002-8085-713X
- Abstract
Inflammasomes represent a group of protein complexes that contribute to host defense against pathogens and repair processes upon the induction of inflammation. However, aberrant and chronic inflammasome activation underlies the pathology of numerous common inflammatory diseases. Inflammasome assembly causes activation of the protease caspase-1 which in turn activates proinflammatory cytokines and induces a lytic type of cell death termed pyroptosis. Although NLRP1 (NACHT, leucine-rich repeat and pyrin domain containing 1) was the first inflammasome sensor, described almost 20 years ago, the molecular mechanisms underlying its activation and the resulting downstream events are incompletely understood. This is partially a consequence of the poor conservation of the NLRP1 pathway between human and mice. Moreover, recent evidence demonstrates a complex and multi-stage mechanism of NLRP1 inflammasome activation. In contrast to other inflammasome sensors, NLRP1 possesses protease activity required for proteolytic self-cleavage and activation mediated by the function-to-find domain (FIIND). CARD8 is a second FIIND protein and is expressed in humans but not in mice. In immune cells and AML (acute myeloid leukemia) cells, the anti-cancer drug talabostat induces CARD8 activation and causes caspase-1-dependent pyroptosis. In contrast, in human keratinocytes talabostat induces NLRP1 activation and massive proinflammatory cytokine activation. NLRP1 is regarded as the principal inflammasome sensor in human keratinocytes and UVB radiation induces its activation, which is believed to underlie the induction of sunburn. Moreover, gain-of-function mutations of NLRP1 cause inflammatory skin syndromes and a predisposition for the development of skin cancer. SNPs (single nucleotide polymorphisms) of NLRP1 are associated with several (auto)inflammatory diseases with a major skin phenotype, such as psoriasis or vitiligo. Here, we summarize knowledge about NLRP1 with emphasis on its role in
- Published
- 2020
10. The NLRP1 Inflammasome in Human Skin and Beyond
- Author
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Fenini, Gabriele, primary, Karakaya, Tugay, additional, Hennig, Paulina, additional, Di Filippo, Michela, additional, and Beer, Hans-Dietmar, additional
- Published
- 2020
- Full Text
- View/download PDF
11. The centrosome protein AKNA regulates neurogenesis via microtubule organization
- Author
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German Research Foundation, Fundación Francisco Cobos, Ministerio de Economía y Competitividad (España), European Research Council, European Commission, National Institutes of Health (US), Camargo Ortega, Germán, Falk, Sven, Johansson, Pia A., Peyre, Elise, Broix, Loïc, Kumar Sahu, Sanjeeb, Hirst, William, Schlichthaerle, Thomas, Juan Romero, Camino de, Draganova, Kalina, Vinopal, Stanislav, Chinnappa, Kaviya, Gavranovic, Anna, Karakaya, Tugay, Steininger, Thomas, Merl-Pham, Juliane, Feederle, Regina, Shao, Wei, Shi, Song-Hai, Hauck, Stefanie M., Jungmann, Ralf, Bradke, Frank, Borrell, Víctor, Geerlof, Arie, Reber, Simone, Tiwari, Vijay K., Huttner, Wieland B., Wilsch-Bräuninger, Michaela, Nguye, Laurent, Götz, Magdalena, German Research Foundation, Fundación Francisco Cobos, Ministerio de Economía y Competitividad (España), European Research Council, European Commission, National Institutes of Health (US), Camargo Ortega, Germán, Falk, Sven, Johansson, Pia A., Peyre, Elise, Broix, Loïc, Kumar Sahu, Sanjeeb, Hirst, William, Schlichthaerle, Thomas, Juan Romero, Camino de, Draganova, Kalina, Vinopal, Stanislav, Chinnappa, Kaviya, Gavranovic, Anna, Karakaya, Tugay, Steininger, Thomas, Merl-Pham, Juliane, Feederle, Regina, Shao, Wei, Shi, Song-Hai, Hauck, Stefanie M., Jungmann, Ralf, Bradke, Frank, Borrell, Víctor, Geerlof, Arie, Reber, Simone, Tiwari, Vijay K., Huttner, Wieland B., Wilsch-Bräuninger, Michaela, Nguye, Laurent, and Götz, Magdalena
- Abstract
The expansion of brain size is accompanied by a relative enlargement of the subventricular zone during development. Epithelial-like neural stem cells divide in the ventricular zone at the ventricles of the embryonic brain, self-renew and generate basal progenitors1 that delaminate and settle in the subventricular zone in enlarged brain regions2. The length of time that cells stay in the subventricular zone is essential for controlling further amplification and fate determination. Here we show that the interphase centrosome protein AKNA has a key role in this process. AKNA localizes at the subdistal appendages of the mother centriole in specific subtypes of neural stem cells, and in almost all basal progenitors. This protein is necessary and sufficient to organize centrosomal microtubules, and promote their nucleation and growth. These features of AKNA are important for mediating the delamination process in the formation of the subventricular zone. Moreover, AKNA regulates the exit from the subventricular zone, which reveals the pivotal role of centrosomal microtubule organization in enabling cells to both enter and remain in the subventricular zone. The epithelial-to-mesenchymal transition is also regulated by AKNA in other epithelial cells, demonstrating its general importance for the control of cell delamination.
- Published
- 2019
12. Efficient Generation of CRISPR/Cas9-Mediated Knockout Human Primary Keratinocytes by Electroporation.
- Author
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Karakaya T, Slaufova M, Di Filippo M, Hennig P, Fenini G, Kündig T, and Beer HD
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- Humans, Cells, Cultured, Cell Differentiation genetics, Cell Culture Techniques methods, CRISPR-Cas Systems, Keratinocytes metabolism, Keratinocytes cytology, Electroporation methods, Gene Knockout Techniques methods, RNA, Guide, CRISPR-Cas Systems genetics, Gene Editing methods
- Abstract
Due to their full differentiation capacity in vitro, the culture of human primary keratinocytes (HPKs) represents a physiological model for answering basic biological and dermatological research questions, including those related to skin diseases and the investigation of treatment options. When modified with the CRISPR/Cas9 gene editing approach and cultivated in organotypic 3D epidermal equivalents (EEs), these human cells have the potential to replace established mouse models. However, even when cultivated on feeder cells, HPKs have only a low proliferation capacity in 2D culture, limiting their application potential. This is particularly true for CRISPR/Cas9-modified HPKs, whose generation commonly requires selection of targeted cells, negatively affecting their lifespan. Here, we describe a robust protocol for the rapid, simple, and efficient generation of single- and multi-gene CRISPR/Cas9 knockout HPKs by electroporation of ribonucleoprotein (RNP) complexes, which comprise one or multiple guide RNAs (gRNAs) and Cas9 protein. Unlike DNA transfection or virus-based targeting strategies, electroporation of RNPs represents a targeting approach that minimizes immunological and toxic side effects. Using efficient gRNAs results in the generation of HPKs with a high yield of knockout cells, allowing for their immediate use in experiments without requiring the laborious process of selecting targeted cells or maintaining a feeder cell culture. Furthermore, the use of RNPs and their delivery via electroporation minimizes off-target and other unspecific effects, preventing unintended genomic alterations. Most importantly, CRISPR/Cas9 knockout HPKs generated with this protocol have the ability to form a fully differentiated epidermis in 3D, thus facilitating the understanding of specific protein functions in a highly physiological human skin model. Alternatively, this approach proves valuable for generating models of mono- or polygenic skin diseases via knockouts, providing insights into the underlying molecular mechanisms and facilitating the development of novel therapeutic approaches., (© 2024. Springer Science+Business Media, LLC.)
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- 2024
- Full Text
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