1,721,007 research outputs found
Transglutaminase type 2: A multifunctional protein chaperone?
No full textMacroautophagy selectively degrades dysfunctional mitochondria by a process known as mitophagy. The purpose of the study published in Cell Death and Differentiation was to investigate the involvement of transglutaminase 2 (TG2) in the turnover and degradation of damaged mitochondria and its effects on cell metabolism
Transglutaminase type 2 in the regulation of proteostasis.
No full textThe maintenance of protein homeostasis (proteostasis) is a fundamental aspect of cell physiology that is essential for the survival of organisms under a variety of environmental and/or intracellular stress conditions. Acute and/or persistent stress exceeding the capacity of the intracellular homeostatic systems results in protein aggregation and/or damaged organelles that leads to pathological cellular states often resulting in cell death. These events are continuously suppressed by a complex macromolecular machinery that uses different intracellular pathways to maintain the proteome integrity in the various subcellular compartments ensuring a healthy cellular life span. Recent findings have highlighted the role of the multifunctional enzyme type 2 transglutaminase (TG2) as a key player in the regulation of intracellular pathways, such as autophagy/mitophagy, exosomes formation and chaperones function, which form the basis of proteostasis regulation under conditions of cellular stress. Here, we review the role of TG2 in these stress response pathways and how its various enzymatic activities might contributes to the proteostasis control
The multifaceted role of HSF1 in pathophysiology: Focus on its interplay with TG2
Full text linkThe cellular environment needs to be strongly regulated and the maintenance of protein homeostasis is crucial for cell function and survival. HSF1 is the main regulator of the heat shock response (HSR), the master pathway required to maintain proteostasis, as involved in the expression of the heat shock proteins (HSPs). HSF1 plays numerous physiological functions; however, the main role concerns the modulation of HSPs synthesis in response to stress. Alterations in HSF1 function impact protein homeostasis and are strongly linked to diseases, such as neurodegenerative disorders, metabolic diseases, and different types of cancers. In this context, type 2 Transglutaminase (TG2), a ubiquitous enzyme activated during stress condition has been shown to promote HSF1 activation. HSF1-TG2 axis regulates the HSR and its function is evolutionary conserved and implicated in pathological conditions. In this review, we discuss the role of HSF1 in the maintenance of proteostasis with regard to the HSF1-TG2 axis and we dissect the stress response pathways implicated in physiological and pathological conditions
Transglutaminase 2 and Ferroptosis: a new liaison?
Full text linkThe recently discovered form of non-apoptotic cell death
program named Ferroptosis is receiving more and more
attention, as stated by increasing number of publications, due to its involvement in both physiological and pathological processes
The role of transglutaminase type 2 in the regulation of autophagy
No full textEukaryotic cells are equipped with a very efficient quality control system to selectively eliminate misfolded and damaged proteins and organelles. Autophagy is the major intracellular degradation/recycling catabolic system for mutated/ misfolded proteins and damaged organelles. It is a highly complex regulated process that plays a key role in cellular maintenance and development. Autophagy is recognized to play an important role in the pathogenesis of the major human diseases. Interestingly, recent studies have demonstrated that autophagy is not a simple metabolite recycling system, but also has the ability to degrade specific cellular targets, such as mitochondria, peroxisomes, cilia, and bacteria. In this chapter the involvement of TG2 in the autophagic pathway is discussed. Indeed, cells or mouse lacking the enzyme show impaired autophagy and accumulate ubiquitinated protein aggregates and damaged mitochondria. TG2 physically interacts with the autophagy cargo protein p62, and they are localized in cytosolic protein aggregates, which are then recruited into autophagosomes where TG2 is degraded. Interestingly, the enzyme’s crosslinking activity is activated during autophagy and its inhibition leads to the accumulation of ubiquitinated proteins indicating that TG2 plays an important role in the assembly of protein aggregates as well as for the clearance of damaged organelles. Interestingly cells lacking the enzyme display impaired autophagy/mitophagy and as a consequence shift their metabolism to glycolysis
Transglutaminase type 2-dependent crosslinking of IRF3 in dying melanoma cells
Full text linkcGAS/STING axis is the major executor of cytosolic dsDNA sensing that leads to the production of type I interferon (IFNI) not only upon bacterial infection, but also in cancer cells, upon DNA damage. In fact, DNA damage caused by ionizing radiations and/or topoisomerase inhibitors leads to a release of free DNA into the cytosol, which activates the cGAS/STING pathway and the induction of IFNI expression. Doxorubicin-induced apoptotic cancer cells release damage-associated molecular patterns (DAMPs), including IFNI, which are able to stimulate the immune system. Our results indicate that Transglutaminase type 2 (TG2) is directly involved in the formation of a covalent cross-linked IRF3 (Interferon regulatory factor 3) dimers, thereby limiting the production of IFNI. Indeed, we demonstrated that upon doxorubicin treatment TG2 translocates into the nucleus of apoptotic melanoma cells interacting with IRF3 dimers. Interestingly, we show that both the knockdown of the enzyme as well as the inhibition of its transamidating activity lead to a decrease in the dimerization of IRF3 correlated with an increase in the IFNI mRNA levels. Taken together, these data demonstrate that TG2 negatively regulates the IRF3 pathway in human melanoma cells suggesting a so far unknown TG2-dependent mechanism by which cancer cells reduce the IFNI production after DNA damage to limit the immune system response
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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