Trk-fused gene plays a critical role in diet-induced adipose tissue expansion and is also involved in thyroid hormone action.

Mutations in the Trk-fused gene (TFG) cause hereditary motor and sensory neuropathy with proximal dominant involvement, which reportedly has high co-incidences with diabetes and dyslipidemia, suggesting critical roles of the TFG in metabolism as well. We found that TFG expression levels in white adipose tissues (WATs) were elevated in both genetically and diet-induced obese mice and that TFG deletion in preadipocytes from the stromal vascular fraction (SVF) markedly inhibited adipogenesis. To investigate its role in vivo, we generated tamoxifen-inducible adipocyte-specific TFG knockout (AiTFG KO) mice.

Auraptene Enhances AMP-Activated Protein Kinase Phosphorylation and Thereby Inhibits the Proliferation, Migration and Expression of Androgen Receptors and Prostate-Specific Antigens in Prostate Cancer Cells.

extract reportedly activates AMPK. Because this extract contains an abundance of auraptene, we investigated whether pure auraptene activates AMPK and inhibits proliferation using prostate cancer cell lines. Indeed, auraptene inhibited the proliferation and migration of LNCaP cells and induced phosphorylation of AMPK or its downstream ACC in LNCaP, PC3, and HEK-293 cells, but not in DU145 cells not expressing LKB1.

Hepatic Pin1 Expression, Particularly in Nuclei, Is Increased in NASH Patients in Accordance with Evidence of the Role of Pin1 in Lipid Accumulation Shown in Hepatoma Cell Lines.

Our previous studies using rodent models have suggested an essential role for Pin1 in the pathogenesis of non-alcoholic steatohepatitis (NASH). In addition, interestingly, serum Pin1 elevation has been reported in NASH patients. However, no studies have as yet examined the Pin1 expression level in human NASH livers.

The expression of prolyl isomerase Pin1 is expanded in the skin of patients with atopic dermatitis and facilitates IL-33 expression in HaCaT cells.

Atopic dermatitis (AD) is attributable to both a genetic predisposition and environmental factors. Among numerous cytokines involved in the pathogenesis of AD, interleukin-33 (IL-33), reportedly escaping exocytotically in response to a scratch, is abundantly expressed in the skin tissues of patients with AD and is postulated to induce inflammatory and autoimmune responses. In this study, we first demonstrated that peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (Pin1), a unique enzyme which isomerizes the proline residues of target proteins, is abundantly expressed in keratinocytes, and that the areas where it is present in the skin tissues of AD patients became expanded due to hyperkeratosis.

Prolyl isomerase Pin1 promotes extracellular matrix production in hepatic stellate cells through regulating formation of the Smad3-TAZ complex.

Hepatic stellate cells (HSCs) produce extracellular matrixes (ECMs), such as collagen and fibronectin, in response to stimulation with transforming growth factor β (TGFβ). The massive ECM accumulation in the liver due to HSCs causes fibrosis which eventually leads to hepatic cirrhosis and hepatoma development. However, details of the mechanisms underlying continuous HSC activation are as yet poorly understood.

Par14 interacts with the androgen receptor, augmenting both its transcriptional activity and prostate cancer proliferation.

Background: Prostate cancer (PCa) is a major cause of cancer morbidity and mortality for men globally, and androgen signaling clearly drives its onset and progression. Androgen receptor (AR) regulation is complex and remains elusive, despite several studies tackling these issues. Therefore, elucidating the mechanism(s) underlying AR regulation is a potentially promising approach to suppressing PCa.

Roles of peptidyl prolyl isomerase Pin1 in viral propagation.

Peptidyl-prolyl isomerase (PPIase) is a unique enzyme that promotes cis-trans isomerization of a proline residue of a target protein. Peptidyl-prolyl cis-trans isomerase NIMA (never in mitosis A)-interacting 1 (Pin1) is a PPIase that binds to the pSer/pThr-Pro motif of target proteins and isomerizes their prolines. Pin1 has been reported to be involved in cancer development, obesity, aging, and Alzheimer's disease and has been shown to promote the growth of several viruses including SARS-CoV-2.

Involvement of neuronal and muscular Trk-fused gene (TFG) defects in the development of neurodegenerative diseases.

Trk-fused gene (TFG) mutations have been identified in patients with several neurodegenerative diseases. In this study, we attempted to clarify the effects of TFG deletions in motor neurons and in muscle fibers, using tissue-specific TFG knockout (vMNTFG KO and MUSTFG KO) mice. vMNTFG KO, generated by crossing TFG floxed with VAChT-Cre, showed deterioration of motor function and muscle atrophy especially in slow-twitch soleus muscle, in line with the predominant Cre expression in slow-twitch fatigue-resistant (S) and fast-twitch fatigue-resistant (FR) motor neurons.

Prolyl isomerase Pin1 plays an essential role in SARS-CoV-2 proliferation, indicating its possibility as a novel therapeutic target.

Novel coronavirus disease 2019 (COVID-19) has emerged as a global pandemic with far-reaching societal impact. Here we demonstrate that Pin1 is a key cellular molecule necessary for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) propagation. In this study, siRNA-mediated silencing of Pin1 expression markedly suppressed the proliferation of SARS-CoV-2 in VeroE6/TMPRSS2 cells.

Synergetic NH absorption properties of the NaBH-LiBH mixed system.

NaBH does not absorb NH below 100 kPa but transforms into a liquid state after NH absorption. On the other hand, LiBH absorbs NH at pressures lower than 100 kPa. Interestingly, mixed borohydrides absorbed NH at low pressures and were liquefied above 100 kPa due to a synergetic phenomenon.

Enhancement of β-xylosidase productivity in cellulase producing fungus Acremonium cellulolyticus.

Enzymatic hydrolysis is one of the most important processes in bioethanol production from lignocellulosic biomass. Acremonium cellulolyticus is a filamentous fungus with high cellulase production but productivity of hemicellulase, especially β-xylosidase, is lower than other filamentous fungi. We identified 2.

The Bdellovibrio bacteriovorus twin-arginine transport system has roles in predatory and prey-independent growth.

Bdellovibrio bacteriovorus grows in one of two ways: either (i) predatorily [in a host-dependent (HD) manner], when it invades the periplasm of another Gram-negative bacterium, exporting into the prey co-ordinated waves of soluble enzymes using the prey cell contents for growth; or (ii) in a host-independent (HI) manner, when it grows (slowly) axenically in rich media. Periplasmic invasion potentially exposes B. bacteriovorus to extremes of pH and exposes the need to scavenge electron donors from prey electron transport components by synthesis of metalloenzymes.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 associates with insulin receptor substrate-1 and enhances insulin actions and adipogenesis.

Peptidyl-prolyl cis/trans isomerase NIMA-interacting 1 (Pin1) is a unique enzyme that associates with the pSer/Thr-Pro motif and catalyzes cis-trans isomerization. We identified Pin1 in the immunoprecipitates of overexpressed IRS-1 with myc and FLAG tags in mouse livers and confirmed the association between IRS-1 and Pin1 by not only overexpression experiments but also endogenously in the mouse liver. The analysis using deletion- and point-mutated Pin1 and IRS-1 constructs revealed the WW domain located in the N terminus of Pin1 and Ser-434 in the SAIN (Shc and IRS-1 NPXY binding) domain of IRS-1 to be involved in their association.

Macrophage foam cell formation is augmented in serum from patients with diabetic angiopathy.

The differentiation of macrophages into cytokine-secreting foam cells plays a critical role in the development of diabetic angiopathy. J774.1, a murine macrophage cell line, reportedly differentiates into foam cells when incubated with oxidized LDL, ApoE-rich VLDL or WHHLMI (myocardial infarction-prone Watanabe heritable hyperlipidemic) rabbit serum.

An unidentified ultraviolet-B-specific photoreceptor mediates transcriptional activation of the cyclobutane pyrimidine dimer photolyase gene in plants.

Cyclobutane pyrimidine dimers (CPDs) constitute a majority of DNA lesions caused by ultraviolet-B (UVB). CPD photolyase, which rapidly repairs CPDs, is essential for plant survival under sunlight containing UVB. Our earlier results that the transcription of the cucumber CPD photolyase gene (CsPHR) was activated by light have prompted us to propose that this light-driven transcriptional activation would allow plants to meet the need of the photolyase activity upon challenges of UVB from sunlight.

Disruption of a gene encoding C4-dicarboxylate transporter-like protein increases ozone sensitivity through deregulation of the stomatal response in Arabidopsis thaliana.

To understand better the plant response to ozone, we isolated and characterized an ozone-sensitive (ozs1) mutant strain from a set of T-DNA-tagged Arabidopsis thaliana ecotype Columbia. The mutant plants show enhanced sensitivity to ozone, desiccation and sulfur dioxide, but have normal sensitivity to hydrogen peroxide, low temperature and high light levels. The T-DNA was inserted at a single locus which is linked to ozone sensitivity.

Salicylic acid accumulation under O3 exposure is regulated by ethylene in tobacco plants.

Ozone (O3), a major photochemical oxidant, induces leaf injury concomitant with salicylic acid (SA) synthesis. In pathogen-infected leaves, SA is synthesized via two pathways, involving phenylalanine or isochorismate. SA biosynthesis under O3 fumigation is not well understood.

Isolation of an ozone-sensitive and jasmonate-semi-insensitive Arabidopsis mutant (oji1).

A novel ozone-sensitive mutant was isolated from Arabidopsis T-DNA tagging lines. This mutant revealed severe foliar injury and higher ethylene emission than the wild type under ozone exposure. The ozone-induced injury and ethylene emission were suppressed by pretreatment with aminoethoxyvinyl glycine, an inhibitor of ethylene biosynthesis, both in this mutant and wild-type plants.

Differential ozone sensitivity among Arabidopsis accessions and its relevance to ethylene synthesis.

We compared the physiological and molecular responses of two Arabidopsis accessions, Col-0 and Ws-2, to ozone (O(3)) exposure. Observation of visible injury as well as ion-leakage analysis demonstrated clear differences between the O(3)-tolerant accession Col and the O(3)-sensitive accession Ws. RNA-blot analysis showed that O(3)-induced increases in mRNA levels of several ethylene-inducible genes and a salicylic acid-inducible gene were substantially higher in Ws than in Col.