Ubiquitin carboxy‐terminal hydrolase <scp>L1</scp> – physiology and pathology

Matuszczak, Ewa; Tylicka, Marzena; Komarowska, Marta; Dębek, Wojciech; Hermanowicz, Adam

doi:10.1002/cbf.3527

Cited by 39 publications

(38 citation statements)

References 89 publications

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“…Our data demonstrate not only that the skin of psoriasis patients expresses lower levels of UCHL1 compared to controls, in agreement with previously published data 32 , but also a clear positive correlation with GADD45a expression. UCHL1 determines cellular levels of ubiquitins and glutathione and regulates cell cycle 33 . Interestingly, it is known that, in keratinocytes, UCHL1 inhibits the secretion of IL-8, IFN-I and MIP3, and suppresses the NF-kβ activity induced by TNF-α 34 .…”

Section: Discussionmentioning

confidence: 99%

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Rodríguez‐Jiménez

Fernández-Messina

Ovejero‐Benito

et al. 2021

Sci Rep

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The interplay between T cells, dendritic cells and keratinocytes is crucial for the development and maintenance of inflammation in psoriasis. GADD45 proteins mediate DNA repair in different cells including keratinocytes. In the immune system, GADD45a and GADD45b regulate the function and activation of both T lymphocytes and dendritic cells and GADD45a links DNA repair and epigenetic regulation through its demethylase activity. Here, we analyzed the expression of GADD45a and GADD45b in the skin, dendritic cells and circulating T cells in a cohort of psoriasis patients and their regulation by inflammatory signals. Thirty patients (17 male/13 female) with plaque psoriasis and 15 controls subjects (7 male/8 female), were enrolled. Psoriasis patients exhibited a lower expression of GADD45a at the epidermis but a higher expression in dermal infiltrating T cells in lesional skin. The expression of GADD45a and GADD45b was also higher in peripheral T cells from psoriasis patients, although no differences were observed in p38 activation. The expression and methylation state of the GADD45a target UCHL1 were evaluated, revealing a hypermethylation of its promoter in lesional skin compared to controls. Furthermore, reduced levels of GADD45a correlated with a lower expression UCHL1 in lesional skin. We propose that the demethylase function of GADD45a may account for its pleiotropic effects, and the complex and heterogeneous pattern of expression observed in psoriatic disease.

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Section: Discussionmentioning

confidence: 99%

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Rodríguez‐Jiménez

Fernández-Messina

Ovejero‐Benito

et al. 2021

Sci Rep

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“…There are many documented roles for these types of proteins, mostly having to do with assessment of cellular ubiquitin and glutathione levels, and regulation of cell cycles. Most interestingly, in regards to the expression trends we see here, is the implication that ubiquitin carboxy-terminal hydrolase can suppress activation of NF-kappaB and increase cellular reactive oxygen species, indicating a possible role in oxidative stress and immune reaction (reviewed in Matuszczak et al, 2020). This protein is also known to play roles in regulation of apoptosis and extrinsic apoptotic signaling and immune defense response.…”

Section: Resultsmentioning

confidence: 68%

Insights into early stages of the establishment of host:algal endosymbioses: Genetic responses to live versus heat-killed algae and bacterial prey in a sponge host

Camilli

Koutsouveli

Hall

et al. 2021

Preprint

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The freshwater sponge Ephydatia muelleri and its Chlorella-like green algal partner is an emerging model for studying animal:algal endosymbiosis. The sponge host is a highly tractable laboratory organism, and the symbiotic algae are easily cultured. We took advantage of these traits to experimentally interrogate fundamental questions about cellular mechanisms that govern the establishment of durable intracellular partnerships between hosts and symbionts in facultative symbioses. We modified a classical experimental approach to discern the phagocytotic mechanisms that might be co-opted to permit persistent infections, and identified genes differentially expressed in E. muelleri sponges early in the establishment of endosymbiosis. We exposed algal-free E. muelleri to live native algal symbionts, native heat-killed algae, and bacteria, and then performed RNASeq so we could compare patterns of gene expression in each treatment. We contrasted differential gene expression patterns between potential food items (bacteria and heat-killed algae) and the live native Chlorella-like symbiont. We found a relatively small but interesting suite of genes that are uniquely and differentially expressed in the host exposed to live algal symbionts, and a larger number of genes uniquely triggered by host exposure to heat-killed algae. One of the host genes, an ABC transporter that is downregulated in response to live algal symbionts, was further evaluated for its possible role in establishment of the algal symbiosis. We discuss the gene expression profiles associated with host responses to living algal cells in the context of conditions necessary for long-term residency within host cells by phototrophic symbionts as well as the genetic responses to sponge phagocytosis and immune driven pathways.

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“…This enzyme likely has both ligase and hydrolase activity to recycle and remove ubiquitin from degraded proteins as well as linking molecules of ubiquitin for tagging proteins to be discarded. The possibility that ubiquitin carboxy-terminal hydrolase can suppress activation of NF-kappaB and increase cellular ROS is particularly interesting, indicating a possible role in oxidative stress and immune reaction (reviewed in Matuszczak et al 2020 ). This protein is also known to play roles in regulation of apoptosis and extrinsic apoptotic signaling and immune defense response.…”

Section: Resultsmentioning

confidence: 99%

Establishment of Host–Algal Endosymbioses: Genetic Response to Symbiont Versus Prey in a Sponge Host

Geraghty

Koutsouveli

Hall

et al. 2021

Genome Biology and Evolution

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The freshwater sponge Ephydatia muelleri and its Chlorella-like algal partner is an emerging model for studying animal: algal endosymbiosis. The sponge host is a tractable laboratory organism, and the symbiotic algae are easily cultured. We took advantage of these traits to interrogate questions about mechanisms that govern the establishment of durable intracellular partnerships between hosts and symbionts in facultative symbioses. We modified a classical experimental approach to discern the phagocytotic mechanisms that might be co-opted to permit persistent infections, and identified genes differentially expressed in sponges early in the establishment of endosymbiosis. We exposed algal-free E. muelleri to live native algal symbionts and potential food items (bacteria and native heat-killed algae), and performed RNA-Seq to compare patterns of gene expression among treatments. We found a relatively small but interesting suite of genes that are differentially expressed in the host exposed to live algal symbionts, and a larger number of genes triggered by host exposure to heat-killed algae. The upregulated genes in sponges exposed to live algal symbionts were mostly involved in endocytosis, ion transport, metabolic processes, vesicle-mediated transport, and oxidation–reduction. One of the host genes, an ATP-Binding Cassette transporter that is downregulated in response to live algal symbionts, was further evaluated for its possible role in the establishment of the symbiosis. We discuss the gene expression profiles associated with host responses to living algal cells in the context of conditions necessary for long-term residency within host cells by phototrophic symbionts as well as the genetic responses to sponge phagocytosis and immune-driven pathways.

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Ubiquitin carboxy‐terminal hydrolase L1 – physiology and pathology

Cited by 39 publications

References 89 publications

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Growth arrest and DNA damage-inducible proteins (GADD45) in psoriasis

Insights into early stages of the establishment of host:algal endosymbioses: Genetic responses to live versus heat-killed algae and bacterial prey in a sponge host

Establishment of Host–Algal Endosymbioses: Genetic Response to Symbiont Versus Prey in a Sponge Host

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