scholarly journals Interaction between Polycomb and SSX Proteins in Pericentromeric Heterochromatin Function and Its Implication in Cancer

Cells ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 226
Author(s):  
Simone Johansen ◽  
Morten Frier Gjerstorff

The stability of pericentromeric heterochromatin is maintained by repressive epigenetic control mechanisms, and failure to maintain this stability may cause severe diseases such as immune deficiency and cancer. Thus, deeper insight into the epigenetic regulation and deregulation of pericentromeric heterochromatin is of high priority. We and others have recently demonstrated that pericentromeric heterochromatin domains are often epigenetically reprogrammed by Polycomb proteins in premalignant and malignant cells to form large subnuclear structures known as Polycomb bodies. This may affect the regulation and stability of pericentromeric heterochromatin domains and/or the distribution of Polycomb factors to support tumorigeneses. Importantly, Polycomb bodies in cancer cells may be targeted by the cancer/testis-related SSX proteins to cause derepression and genomic instability of pericentromeric heterochromatin. This review will discuss the interplay between SSX and Polycomb factors in the repression and stability of pericentromeric heterochromatin and its possible implications for tumor biology.

2019 ◽  
Vol 47 (13) ◽  
pp. 6668-6684 ◽  
Author(s):  
Sofie Traynor ◽  
Niels Erik Møllegaard ◽  
Mikkel G Jørgensen ◽  
Nadine H Brückmann ◽  
Christina B Pedersen ◽  
...  

AbstractRearrangement of the 1q12 pericentromeric heterochromatin and subsequent amplification of the 1q arm is commonly associated with cancer development and progression and may result from epigenetic deregulation. In many premalignant and malignant cells, loss of 1q12 satellite DNA methylation causes the deposition of polycomb factors and formation of large polycomb aggregates referred to as polycomb bodies. Here, we show that SSX proteins can destabilize 1q12 pericentromeric heterochromatin in melanoma cells when it is present in the context of polycomb bodies. We found that SSX proteins deplete polycomb bodies and promote the unfolding and derepression of 1q12 heterochromatin during replication. This further leads to segregation abnormalities during anaphase and generation of micronuclei. The structural rearrangement of 1q12 pericentromeric heterochromatin triggered by SSX2 is associated with loss of polycomb factors, but is not mediated by diminished polycomb repression. Instead, our studies suggest a direct effect of SSX proteins facilitated though a DNA/chromatin binding, zinc finger-like domain and a KRAB-like domain that may recruit chromatin modifiers or activate satellite transcription. Our results demonstrate a novel mechanism for generation of 1q12-associated genomic instability in cancer cells.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Kiran Todkar ◽  
Lilia Chikhi ◽  
Véronique Desjardins ◽  
Firas El-Mortada ◽  
Geneviève Pépin ◽  
...  

AbstractMost cells constitutively secrete mitochondrial DNA and proteins in extracellular vesicles (EVs). While EVs are small vesicles that transfer material between cells, Mitochondria-Derived Vesicles (MDVs) carry material specifically between mitochondria and other organelles. Mitochondrial content can enhance inflammation under pro-inflammatory conditions, though its role in the absence of inflammation remains elusive. Here, we demonstrate that cells actively prevent the packaging of pro-inflammatory, oxidized mitochondrial proteins that would act as damage-associated molecular patterns (DAMPs) into EVs. Importantly, we find that the distinction between material to be included into EVs and damaged mitochondrial content to be excluded is dependent on selective targeting to one of two distinct MDV pathways. We show that Optic Atrophy 1 (OPA1) and sorting nexin 9 (Snx9)-dependent MDVs are required to target mitochondrial proteins to EVs, while the Parkinson’s disease-related protein Parkin blocks this process by directing damaged mitochondrial content to lysosomes. Our results provide insight into the interplay between mitochondrial quality control mechanisms and mitochondria-driven immune responses.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Oleg Shuvalov ◽  
Alyona Kizenko ◽  
Alexey Petukhov ◽  
Olga Fedorova ◽  
Alexandra Daks ◽  
...  

AbstractCancer-testicular Antigens (CTAs) belong to a group of proteins that under normal conditions are strictly expressed in a male’s reproductive tissues. However, upon malignisation, they are frequently re-expressed in neoplastic tissues of various origin. A number of studies have shown that different CTAs affect growth, migration and invasion of tumor cells and favor cancer development and metastasis. Two members of the CTA group, Semenogelin 1 and 2 (SEMG1 and SEMG2, or SEMGs) represent the major component of human seminal fluid. They regulate the motility and capacitation of sperm. They are often re-expressed in different malignancies including breast cancer. However, there is almost no information about the functional properties of SEMGs in cancer cells. In this review, we highlight the role of SEMGs in the reproductive system and also summarize the data on their expression and functions in malignant cells of various origins.


2002 ◽  
Vol 74 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Lanny S. Liebeskind ◽  
Jiri Srogl ◽  
Cecile Savarin ◽  
Concepcion Polanco

Given the stability of the bond between a mercaptide ligand and various redox-active metals, it is of interest that Nature has evolved significant metalloenzymatic processes that involve key interactions of sulfur-containing functionalities with metals such as Ni, Co, Cu, and Fe. From a chemical perspective, it is striking that these metals can function as robust biocatalysts in vivo, even though they are often "poisoned" as catalysts in vitro through formation of refractory metal thiolates. Insight into the nature of this chemical discrepancy is under study in order to open new procedures in synthetic organic and organometallic chemistry.


Development ◽  
1972 ◽  
Vol 28 (3) ◽  
pp. 521-546
Author(s):  
G. V. Lopashov ◽  
Alla A. Sologub

The present work was aimed at investigating the possibility and conditions necessary for the artificial transformation of one tissue into another. Experiments were carried out with the pigmented epithelium of the eye in tadpoles and adult frogs of Rana temporaria. Following the removal of the mesenchyme envelopes (or their exfoliation during the experiment), pigmented epithelium transformed into retina under the influence of retina from tadpoles of the same species. This phenomenon was observed both under the cultivation of a piece of retina in a sandwich of pigmented epithelium and the transplantation of pigmented epithelium layers into the eye cavity of tadpoles. Such transformation did not occur in the absence of retinal influence. Metaplasia requires the removal of the mesenchyme envelopes, the action of the retinal agent, as well as preservation of the integrity of the pigmented epithelium layer and subsequent proliferation of its cells. The character of general control mechanisms both maintaining the stability of cell types and leading to their transformation into other cell types is discussed.


2016 ◽  
Vol 8 (3) ◽  
pp. 5
Author(s):  
Jirí Stavek

<p class="1Body">An attempt is presented for the description of the spectral colors using the standard trigonometric tools in order to extract more information about photons. We have arranged the spectral colors on an arc of the circle with the radius R = 1 and the central angle θ = π/3 when we have defined cos (θ) = λ<sub>380</sub>/λ<sub>760</sub> = 0.5. Several trigonometric operations were applied in order to find the gravity centers for the scotopic, photopic, and mesopic visions. The concept of the center of gravity of colors introduced Isaac Newton. We have postulated properties of the long-lived photons with the new interpretation of the Hubble (Zwicky-Nernst) constant H<sub>0</sub> = 2.748… * 10<sup>-18</sup> kg kg<sup>-1 </sup>s<sup>-1</sup>, the specific mass evaporation rate (SMER) of gravitons from the source mass. The stability of international prototypes of kilogram has been regularly checked. We predict that those standard kilograms due to the evaporation of gravitons lost 8.67 μg kg<sup>-1</sup> century<sup>-1</sup>. The energy of long-lived photons was trigonometrically decomposed into three parts that could be experimentally tested: longitudinal energy, transverse energy and energy of evaporated gravitons. We tested the properties of the long-lived photons with the experimental data published for the best available standard candles: supernovae Type Ia. There was found a surprising match of those experimental data with the model of the long-lived photons. Finally, we have proposed a possible decomposition of the big G (Newtonian gravitational constant) and the small kappa κ (Einsteinian gravitational constant) in order to get a new insight into the mysterious gravitational force and/or the curvature concept.</p>


2021 ◽  
Vol 10 (1) ◽  
pp. 37-40
Author(s):  
Vesna Savić ◽  
Milica Martinović ◽  
Ivana Nešić ◽  
Jelena Živković ◽  
Ivana Gajić

The aim of this study was to compare the stability and texture of three zinc oxide suspensions with different additives. Suspension 1 was made as official magistral formulation Suspensio album 7.5% from Formulae magistrales 2008. Suspension 2 was prepared when 1% carbomer gel was added to suspension 1 and suspension 3 was prepared when polysorbate 20 was added to suspension 2. After stability tests, texture analysis was performed on all suspensions. Following parameters were measured: hardness cycle 1, hardness cycle 2, cohesiveness, adhesiveness, resilience and springiness. The study showed that suspension 3 had the lowest value of hardness, and therefore the best spreadability. Also, suspension 3 was the least sticky of all three, since it was characterized with the lowest adhesiveness. Further, suspension 3 was the most cohesive and is predicted to withstand the stress during packing and use longer than others. On the other hand, the highest values of resilience and springiness were detected for suspension 1, while the lowest was related to suspension 2. Therefore, the best textural characteristics were assigned to suspension 3. This result is in accordance with the results of performed stability tests. The results of our study offer insight into potential improvements of the current magistral formulation Suspensio album 7.5%.


Author(s):  
Rajesh Heynickx

In this article it is demonstrated that an analysis of how building metaphorswere used in the Flemish Catholic discourse of the interwar years can offermore insight into the way a community of believers tries to establish a culturalcohesiveness. The main argument is that in a period of deep transformations,building metaphors could become "instruments" for Catholics whowanted to defend and promote a traditional dimension of their religion.Building metaphors allowed Catholics to stress the stability of their own ideology(the fundaments) and to formulate their own cultural project (buildingplan). By analysing such strategic use of building metaphors in artistic andphilosophical discourses, it can become possible to shed more light on the roleneo-thomism, a main philosophical current in interwar Flanders, played inartistic debates and more specific in discussions on the modernisation of religiousart.


ChemSusChem ◽  
2020 ◽  
Vol 13 (17) ◽  
pp. 4743-4758
Author(s):  
Yannick Mathieu ◽  
Juan D. Vidal ◽  
Lourdes Arribas Martínez ◽  
Nerea Abad Fernández ◽  
Sara Iborra ◽  
...  

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